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.

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.

Acute Ingestion of A Novel Nitrate-Rich Dietary Supplement Significantly Increases Plasma Nitrate/Nitrite in Physically Active Men and Women.

BACKGROUND: Dietary supplements purported to increase circulating nitric oxide are very popular among consumers. We determined the acute impact of two novel dietary supplements on plasma nitrate/nitrite (NOx) and nitrite alone. METHODS: 20 men and women (age: 24 ± 5 years) ingested two different nitrate-rich supplements (Resync Recovery Blend at 7.5 g and 15 g; Resync Collagen Blend at 21 g), or placebo, on four different days. Fasting blood samples were obtained before and 75 min following ingestion and analyzed for NOx and nitrite. RESULTS: Nitrite was not differently impacted by treatment (p > 0.05). The NOx response for men and women was very similar, with no sex interactions noted (p > 0.05). Condition (p < 0.0001), time (p < 0.0001), and condition x time (p < 0.0001) effects were noted for NOx. Values increased from baseline to post-ingestion for the Resync Recovery Blend at 7.5 g (11 ± 9 to 101 ± 48 µM) and at 15 g (9 ± 5 to 176 ± 91µM), as well as for the Resync Collagen Blend (9 ± 9 to 46 ± 21µM), while values for placebo remained stable (9 ± 7 to 8 ± 5µM). CONCLUSION: While nitrite alone was not impacted by treatment, both Resync products result in an increase in plasma NOx, with the increase proportionate to the quantity of "nitric oxide blend" ingredients contained within each product. Future studies are needed to determine the physiological implications of the increased NOx, as pertaining to exercise performance and recovery, in addition to other aspects of human health.

Effects of Curcumin on the Oxidative Stress Response to a Dual Stress Challenge in Trained Men.

Firefighters and military personnel are exposed to a variety of stressors. The combination of mental and physical stress (i.e., dual stress challenges [DSCs]) results in significant oxidative stress (OS), which may contribute to cardiometabolic dysfunction. Curcumin (CUR) is an exogenous antioxidant that may attenuate such OS. Fourteen trained men participated in a randomized, cross-over design to investigate the impact of CUR on markers of OS resulting from DSC. CUR or placebo was ingested three days prior to, and the morning of, testing. The DSC involved 20 min of mental stress challenges during 35 min of cycling at 60% V̇O2 peak. Blood was sampled before, as well as immediately, 30 min, and 60 min after, exercise and analyzed for glutathione (GSH), superoxide dismutase (SOD), hydrogen peroxide (H2O2), and advanced oxidation protein products (AOPP). There was no treatment effect for any variable. However, the DSC resulted in significant reductions in SOD, H2O2, and AOPP at 30 and 60 min after exercise. Previous studies have shown that DSC results in significant OS compared to exercise alone. However, these data suggest the DSC was associated with reductions in postexercise markers of OS. Antioxidant therapy is likely not needed in trained men exposed to DSC.

Acute coffee ingestion with and without medium-chain triglycerides decreases blood oxidative stress markers and increases ketone levels.

Ingestion of ketone supplements, caffeine, and medium-chain triglycerides (MCTs) may all be effective strategies to increase blood levels of the ketone body beta-hydroxybutyrate (D-BHB). However, acute ingestion of a bolus of lipids may increase oxidative stress (OS). The purpose of the study was to investigate the impact of adding varying amounts of MCTs to coffee on blood levels of D-BHB and markers of OS. Ten college-aged men ingested coffee with 0, 28, and 42 g of MCT in a randomized order. Blood samples were collected pre- as well as 2 and 4 h postprandial and analyzed for D-BHB, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), glucose, triglycerides (TAG), insulin, and OS markers: advanced oxidation protein products (AOPP), glutathione (GSH), malondialdehyde (MDA), and hydrogen peroxide (H2O2). All three treatments resulted in a significant increase in D-BHB, HDL-c, and TC as well as a significant decrease in TAG, MDA, H2O2, and insulin. The 42 g treatment was associated with significantly higher levels of AOPP and MDA. Acute ingestion of coffee results in favorable changes to markers of cardiometabolic health that were not impacted by the addition of 28 g of MCT. However, 42 g of MCT caused significantly greater OS.

A Comparison of Dietary and Caloric Restriction Models on Body Composition, Physical Performance, and Metabolic Health in Young Mice.

Time-restricted feeding (TRF), alternate day fasting (ADF), and the dietary restriction model known as the Daniel Fast (DF; a vegan/non-processed food diet plan) have garnered attention recently as nutritional interventions to combat obesity. We compared the effects of various dietary models on body composition, physical performance, and metabolic health in C57BL/6 mice. Sixty young C57BL/6 male mice were assigned a diet of TRF, ADF, DF, caloric restriction (CR), a high-fat Western diet (HF) fed ad libitum, or standard rodent chow for eight weeks. Their body composition, run time to exhaustion, fasting glucose, insulin, and glucose tolerance test area under the glucose curve (AUC) were determined. Compared to the HF group, all groups displayed significantly less weight and fat mass gain, as well as non-significant changes in fat-free mass. Additionally, although not statistically significant, all groups displayed greater run time to exhaustion relative to the HF group. Compared to the HF group, all groups demonstrated significantly lower fasting glucose, insulin, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), as well as improved glucose tolerance, and the ADF group displayed the best fasting glucose and glucose tolerance results, with DF having the best HOMA-IR. All investigated fasting protocols may improve body composition, measures of insulin sensitivity, and physical performance compared to a high-fat Western diet. The DF and ADF protocols are most favorable with regards to insulin sensitivity and glucose tolerance. Since our selected dietary protocols have also been investigated in humans with success, it is plausible to consider that these dietary models could prove beneficial to men and women seeking improved body composition and metabolic health.

Effects of psychological stress during exercise on markers of oxidative stress in young healthy, trained men.

PURPOSE: Those engaged in high stress occupations such as firefighters and military personnel are exposed to a variety of psychological and physiological stressors. The combination of mental and physical stress [i.e., dual stress challenges (DSC)] results in significant increases in stress hormones, which causes oxidative stress (OS) and contributes to elevated risk for cardiovascular disease. However, data are needed to determine the impact of DSC on markers of OS in exercise-trained individuals. METHOD: Fourteen healthy trained men aged 21-30 yrs. participated in a randomized, cross-over design to investigate the impact of DSC on blood markers of OS. The exercise alone condition (EA) consisted of 35 min of cycling at 60% V̇O2 peak. The DSC involved 20 min of mental stress challenges during exercise. Blood was sampled before exercise, as well as immediately, and 30 and 60 min after exercise and analyzed for glutathione (GSH), superoxide dismutase (SOD), hydrogen peroxide (H2O2) and advanced oxidation protein products (AOPP). RESULT: No significant treatment × time interactions were found. No time effects were noted for SOD, or H2O2; however, AOPP were reduced at 30 (p = .034) and 60 min post exercise (p = .006). GSH was reduced at 30 (p = .009) and 60 min post exercise (p = .031). CONCLUSION: These results indicate the OS response from DSC is not greater than that produced from EA in exercise trained men. Future work should investigate the impact of chronic resistance and endurance exercise training on OS resulting from DSC.

Effects of Environmental Heat and Antioxidant Ingestion on Blood Markers of Oxidative Stress in Professional Firefighters Performing Structural Fire Exercises.

OBJECTIVE: Firefighters (FFs) involved in fire suppression have the greatest on-duty risk of cardiovascular disease (CVD), which may be caused by oxidative stress (OS). METHODS: Healthy, active FFs performed a victim "search and clear" exercise involving three conditions: (1) no heat, (2) heat + antioxidant, and (3) heat + placebo. Blood samples were analyzed for OS markers glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), catalase (CAT), and advanced oxidation protein products (AOPP). RESULTS: Increased GSH was found during both heat conditions compared with no heat. CAT activity was higher immediately post exercise. AOPP was reduced post exercise. CONCLUSIONS: Antioxidant supplementation did not impact the OS response to exercise. Added heat did not cause OS and exercise resulted in reductions in OS markers. These findings can be attributed to the training status of the FFs involved.

Modulation of endoplasmic reticulum stress and the unfolded protein response in cancerous and noncancerous cells.

OBJECTIVES: The bio-field array is a device that generates a dielectrophoretic electromagnetic field when placed in a hypotonic saline solution and a direct current of approximately 3 A is applied. It is known that cell physiology is guided by bioelectrical properties, and there is a significant growth inhibition in cancerous (MDA-MB-231) cells that are grown in media that has been reconstituted with the saline that has been exposed to the bio-field array direct current dielectrophoretic electromagnetic field, alternatively there is no growth inhibition noted in noncancerous cells (MCF-10A) when grown in the bio-field array direct current dielectrophoretic electromagnetic field treated versus control media. METHODS: To examine the basis for selective growth inhibition in human breast carcinoma, we employed cell death assays, cell cycle assays, microarray analysis and reverse transcription-quantitative polymerase chain reaction. RESULTS: We found a large transcriptional reprogramming in the cell lines and of the genes affected, those involved in endoplasmic reticulum stress and the unfolded protein response pathways showed some of the most dramatic changes. Cancerous cells grown in media that has been reconstituted with a hypotonic saline solution that has been exposed to the bio-field array direct current dielectrophoretic electromagnetic field show a significant and strong upregulation of the apoptotic arms of the unfolded protein response while the noncancerous cells show a decrease in endoplasmic reticulum stress via microarray analyses and reverse transcription-quantitative polymerase chain reaction. CONCLUSION: The bio-field array shows potential to initiate apoptosis in cancerous cells while relieving cell stress in noncancerous cells in vitro. These studies lay a foundation for nurses to conduct future in vivo models for the possible development of future adjunct treatments in chronic disease.

Bio-field array: a dielectrophoretic electromagnetic toroidal excitation to restore and maintain the golden ratio in human erythrocytes.

Erythrocytes must maintain a biconcave discoid shape in order to efficiently deliver oxygen (O2 ) molecules and to recycle carbon dioxide (CO2 ) molecules. The erythrocyte is a small toroidal dielectrophoretic (DEP) electromagnetic field (EMF) driven cell that maintains its zeta potential (ζ) with a dielectric constant (ԑ) between a negatively charged plasma membrane surface and the positively charged adjacent Stern layer. Here, we propose that zeta potential is also driven by both ferroelectric influences (chloride ion) and ferromagnetic influences (serum iron driven). The Golden Ratio, a function of Phi φ, offers a geometrical mathematical measure within the distinct and desired curvature of the red blood cell that is governed by this zeta potential and is required for the efficient recycling of CO2 in our bodies. The Bio-Field Array (BFA) shows potential to both drive/fuel the zeta potential and restore the Golden Ratio in human erythrocytes thereby leading to more efficient recycling of CO2 . Live Blood Analyses and serum CO2 levels from twenty human subjects that participated in immersion therapy sessions with the BFA for 2 weeks (six sessions) were analyzed. Live Blood Analyses (LBA) and serum blood analyses performed before and after the BFA immersion therapy sessions in the BFA pilot study participants showed reversal of erythrocyte rheological alterations (per RBC metric; P = 0.00000075), a morphological return to the Golden Ratio and a significant decrease in serum CO2 (P = 0.017) in these participants. Immersion therapy sessions with the BFA show potential to modulate zeta potential, restore this newly defined Golden Ratio and reduce rheological alterations in human erythrocytes.

Time-restricted feeding of a high-fat diet in male C57BL/6 mice reduces adiposity but does not protect against increased systemic inflammation.

Time-restricted feeding (TRF) limits the duration of food availability without altering diet composition and can combat obesity in humans and mice. For this study we evaluated the effect of timing of food access during a TRF protocol on weight gain, adiposity, and inflammation. Young male C57BL/6 mice were placed on a high-fat (HF) diet (45% fat) for 8 weeks. Food access was unrestricted (HF) or restricted to 6 h per day, either for the first half (HF-early) or the second half (HF-late) of the active phase to resemble a window of time for food consumption early or late in the day in a human population. Weight, obesity-associated parameters, and inflammation were measured. TRF reduced weight gain over the 8-week period in mice consuming the same high-fat diet. Consistent with decreased weight gain in the TRF groups, body fat percentage, liver triglycerides, and plasma leptin and cholesterol levels were reduced. Adipose tissue inflammation, measured by CD11b+F4/80+ macrophage infiltration, was reduced in both TRF groups, but systemic tumor necrosis factor-α was increased in all groups consuming the high-fat diet. The HF-late group gained more weight than the HF-early group and had increased insulin resistance, while the HF-early group was protected. Therefore, a TRF protocol is beneficial for weight management when a high-fat diet is consumed, with food consumption earlier in the day showing greater health benefits. However, increased inflammatory markers in the TRF groups suggest that diet components can still increase inflammation even in the absence of overt obesity.

Assessment of the Drug-Drug Interaction Potential Between Theacrine and Caffeine in Humans.

Objective: Theacrine, a methylurate class purine alkaloid, triggers diverse pharmacologic responses, including psychostimulatory activity by modulation of adenosinergic and dopaminergic pathways. In a double-blind, placebo-controlled study, theacrine increased energy, concentration, and mood, while reducing fatigue. Because caffeine, a methylxanthine purine alkaloid, is frequently coadministered with theacrine, we sought to determine if a pharmacokinetic and/or pharmacodynamic interaction existed between theacrine and caffeine. Methods: Eight healthy adults received theacrine, as TeaCrine® (25 or 125 mg), caffeine (150 mg), or a combination of theacrine (125 mg) and caffeine (150 mg) in a randomized, double-blind crossover study. Blood samples were collected over a 24-hour period and analyzed by Liquid chromatrography-mass spectrometry/mass spectrometry (LC-MS/MS) for theacrine, caffeine, and paraxanthine. Pharmacodynamic response markers, heart rate and blood pressure, were recorded. Results: Theacrine pharmacokinetics was similar following administration of theacrine alone. Caffeine coadministration increased maximum plasma concentration and area under the curve of theacrine without altering theacrine half-life. Theacrine had no impact on caffeine or paraxanthine pharmacokinetics. There was no difference between treatment groups with regard to heart rate or systolic/diastolic blood pressure. Conclusions: Coadministration of theacrine and caffeine results in a clinically significant pharmacokinetic interaction, viz., increased theacrine exposure. Enhanced oral bioavailability is the most likely mechanism by which caffeine alters theacrine exposure. However, further studies examining the contribution of presystemic elimination mechanisms, for example, efflux transport and/or gut metabolism, to theacrine bioavailability are needed to confirm the exact mechanism(s). Hemodynamic parameters were unaltered despite the pharmacokinetic interaction, suggesting that coadministration of caffeine and theacrine is safe at the doses administered.

Methylsulfonylmethane: Applications and Safety of a Novel Dietary Supplement.

Methylsulfonylmethane (MSM) has become a popular dietary supplement used for a variety of purposes, including its most common use as an anti-inflammatory agent. It has been well-investigated in animal models, as well as in human clinical trials and experiments. A variety of health-specific outcome measures are improved with MSM supplementation, including inflammation, joint/muscle pain, oxidative stress, and antioxidant capacity. Initial evidence is available regarding the dose of MSM needed to provide benefit, although additional work is underway to determine the precise dose and time course of treatment needed to provide optimal benefits. As a Generally Recognized As Safe (GRAS) approved substance, MSM is well-tolerated by most individuals at dosages of up to four grams daily, with few known and mild side effects. This review provides an overview of MSM, with details regarding its common uses and applications as a dietary supplement, as well as its safety for consumption.

Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress.

The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida's southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (p<0.05) in lymphocyte proliferation were observed in ConA and PHA stimulated lymphocytes from rescued animals compared to non-exposed animals. Significant correlations were observed between oxidative stress markers (SOD, ROS/RNS) and plasma brevetoxin concentrations. Sublethal exposure to brevetoxins in the wild impacts some immune function components, and thus, overall health, in the Florida manatee.