Medical Marijuana, Recreational Cannabis, and Cardiovascular Health: A Scientific Statement From the American Heart Association.

Cannabis, or marijuana, has potential therapeutic and medicinal properties related to multiple compounds, particularly Δ-9-tetrahydrocannabinol and cannabidiol. Over the past 25 years, attitudes toward cannabis have evolved rapidly, with expanding legalization of medical and recreational use at the state level in the United States and recreational use nationally in Canada and Uruguay. As a result, the consumption of cannabis products is increasing considerably, particularly among youth. Our understanding of the safety and efficacy of cannabis has been limited by decades of worldwide illegality and continues to be limited in the United States by the ongoing classification of cannabis as a Schedule 1 controlled substance. These shifts in cannabis use require clinicians to understand conflicting laws, health implications, and therapeutic possibilities. Cannabis may have therapeutic benefits, but few are cardiovascular in nature. Conversely, many of the concerning health implications of cannabis include cardiovascular diseases, although they may be mediated by mechanisms of delivery. This statement critically reviews the use of medicinal and recreational cannabis from a clinical but also a policy and public health perspective by evaluating its safety and efficacy profile, particularly in relationship to cardiovascular health.

Acute dietary nitrate does not reduce resting metabolic rate or oxidative stress marker 8-isoprostane in healthy males and females.

To investigate changes in resting metabolic rate and 8-isoprostane, an oxidative stress biomarker, following acute dietary nitrate supplementation in healthy males and females. In a randomised, double-blind, cross-over study, 10 males and seven females (age range 19-25 years) underwent protocol familiarisation (visit 1), baseline assessments (visits 2 and 4) and assessments following supplementation, placebo or 6.2 mmol nitrate, 2 hours prior to visits 3 and 5. Participants completed a 30-minute RMR test with visits 2 and 3 on consecutive days, separated by a week-long washout period concluding with visits 4 and 5 on consecutive days. Plasma nitrate/nitrite (NOx) significantly increased (p ≤ 0.05) following dietary nitrate consumption compared to baseline values. No significant effect on resting metabolism (p = 0.194) or 8-isoprostane (p = 0.660) was observed following dietary nitrate supplementation. Dietary nitrate increases NO bioavailability, but acute supplementation does not effect resting metabolism or 8-isoprostane in healthy males and females.

The absorptive effects of orobuccal non-liposomal nano-sized glutathione on blood glutathione parameters in healthy individuals: A pilot study.

BACKGROUND: Glutathione is an endogenous antioxidant found in oxidized (GSSG) and reduced (GSH) forms. Glutathione depletion is indicative of oxidative stress and occurs in various pathological conditions and following extreme exercise activity. Raising blood glutathione concentration has potential to attenuate and prevent chronic disease and also to improve recovery from exercise. There are a number of challenges to achieving this through traditional dietary supplements, and thus there is a need to develop optimized delivery methods to improve blood glutathione status. This study evaluated the effect of a novel glutathione formulation on blood glutathione parameters in healthy individuals. METHODS: 15 (8 male) healthy individuals (25±5y old, 78.0±14.6kg) participated in a single-blinded randomized placebo-controlled crossover study, with a minimum one-week washout period between treatments. Participants were overnight fasted and administered 1mL of a non-liposomal nano-size glutathione solution (NLNG) containing 200mg of glutathione or 1mL of placebo lacking glutathione. The solution was held in the mouth for 90 seconds before the remainder was swallowed. Blood was collected at baseline, 5, 10, 30, 60 and 120 minutes post-treatment. Protein-bound plasma and erythrocyte lysate concentrations of GSH and GSSG were measured at all time points using previously validated procedures. Linear mixed effects models were used to compare differences between baseline and post-treatment glutathione concentrations between NLNG and placebo for each parameter. RESULTS: There was a significant main effect for treatment type, such that increases in GSH concentration in erythrocyte lysate were greater following NLNG than placebo (p = 0.001). Similar significant main effects for treatment were also found for total (protein bound + erythrocyte lysate) GSH (p = 0.015) and GSSG (p = 0.037) concentration, as well as total blood glutathione pool (GSH+GSSG, p = 0.006). DISCUSSION: NLNG increased multiple blood glutathione parameters compared to placebo. Future research should examine whether NLNG can attenuate oxidative stress.

Acute dietary nitrate supplementation does not attenuate oxidative stress or the hemodynamic response during submaximal exercise in hypobaric hypoxia.

The purpose of this study was to investigate changes in oxidative stress, arterial oxygen saturation (SaO2), blood pressure (BP), and heart rate (HR) during exercise in hypobaric hypoxia following acute dietary nitrate supplementation. Nine well-trained (maximal oxygen consumption, 60.8 ± 7.8 mL·kg-1·min-1) males (age, 29 ± 7 years) visited the laboratory on 3 occasions, each separated by 1 week. Visit 1 included a maximal aerobic cycling test and five 5-min increasing-intensity exercise bouts in a normobaric environment (1600 m). A single dose of either a nitrate-depleted placebo (PL) or a nitrate-rich beverage (NR; 12.8 mmol nitrate) was consumed 2.5 h prior to exercise during visits 2 and 3 (3500 m) in a double-blind, placebo-controlled, crossover study consisting of a 5-min cycling warm-up and 4 bouts, each 5 min in duration, separated by 4-min periods of passive rest. Exercise wattages were determined during visit 1 and corresponded to 25%, 40%, 50%, 60%, and 70% of normobaric maximal oxygen consumption. Catalase and 8-isoprostane were measured before and after exercise (immediately before and 1 h postexercise, respectively). NR increased plasma nitrite (1.53 ± 0.83 µmol·L-1) compared with PL (0.88 ± 0.56 µmol·L-1) (p < 0.05). In both conditions, postexercise (3500 m) 8-isoprostane (PL, 23.49 ± 3.38 to 60.90 ± 14.95 pg·mL-1; NR, 23.23 ± 4.12 to 52.11 ± 19.76 pg·mL-1) and catalase (PL, 63.89 ± 25.69 to 128.15 ± 41.80 mmol·min-1·mL-1; NR, 78.89 ± 30.95 to 109.96 ± 35.05 mmol·min-1·mL-1) were elevated compared with baseline resting values (p < 0.05). However, both 8-isoprostane and catalase were similar in the 2 groups (PL and NR) (p = 0.217 and p = 0.080, respectively). We concluded that an acute, pre-exercise dose of dietary nitrate yielded no beneficial changes in oxidative stress, SaO2, BP, or HR in healthy, aerobically fit men exercising at 3500 m.

Components of Fatigue: Mind and Body.

Carriker, CR. Components of fatigue: mind and body. J Strength Cond Res 31(11): 3170-3176, 2017-Maximal intensity exercise requires significant energy demand. Subsequently, prolonged high-intensity effort eventually initiates volitional cessation of the event; often preceeded by a sensation of fatigue. Those examining the basis of fatigue tend to advocate either a peripheral or central model to explain such volitional failure. Practitioners and athletes who understand the tenants of fatigue can tailor their exercise regimens to target areas of potential physical or mental limitation. This review examines the rationale surrounding 2 separate models which postulate the origination of fatigue. Although the peripheral model suggests that fatigue occurs at the muscles, others have suggested a teloanticipatory cognitive component which plays a dominant role. Those familiar with both models may better integrate practice-based evidence into evidence-based practice. The highly individual nature of human performance further highlights the compulsion to comprehend the spectrum of fatigue, such that the identification of insufficiencies should mandate the development of a training purview for peak human performance.

Nitrate-containing beetroot enhances myocyte metabolism and mitochondrial content.

Beetroot ( tián cài) juice consumption is of current interest for improving aerobic performance by acting as a vasodilator and possibly through alterations in skeletal muscle metabolism and physiology. This work explored the effects of a commercially available beetroot supplement on metabolism, gene expression, and mitochondrial content in cultured myocytes. C2C12 myocytes were treated with various concentrations of the beetroot supplement for various durations. Glycolytic metabolism and oxidative metabolism were quantified via measurement of extracellular acidification and oxygen consumption, respectively. Metabolic gene expression was measured using quantitative reverse transcription-polymerase chain reaction, and mitochondrial content was assessed with flow cytometry and confocal microscopy. Cells treated with beetroot exhibited significantly increased oxidative metabolism, concurrently with elevated metabolic gene expression including peroxisome proliferator-activated receptor gamma coactivator-1 alpha, nuclear respiratory factor 1, mitochondrial transcription factor A, and glucose transporter 4, leading to increased mitochondrial biogenesis. Our data show that treatment with a beetroot supplement increases basal oxidative metabolism. Our observations are also among the first to demonstrate that beetroot extract is an inducer of metabolic gene expression and mitochondrial biogenesis. These observations support the need for further investigation into the therapeutic and pharmacological effects of nitrate-containing supplements for health and athletic benefits.

Effect of Acute Dietary Nitrate Consumption on Oxygen Consumption During Submaximal Exercise in Hypobaric Hypoxia.

Reduced partial pressure of oxygen impairs exercise performance at altitude. Acute nitrate supplementation, at sea level, may reduce oxygen cost during submaximal exercise in hypobaric hypoxia. Therefore, we investigated the metabolic response during exercise at altitude following acute nitrate consumption. Ten well-trained (61.0 ± 7.4 ml/kg/min) males (age 28 ± 7 yr) completed 3 experimental trials (T1, T2, T3). T1 included baseline demographics, a maximal aerobic capacity test (VO2max) and five submaximal intensity cycling determination bouts at an elevation of 1600 m. A 4-day dietary washout, minimizing consumption of nitrate-rich foods, preceded T2 and T3. In a randomized, double-blind, placebo-controlled, crossover fashion, subjects consumed either a nitrate-depleted beetroot juice (PL) or ~12.8 mmol nitrate rich (NR) beverage 2.5 hr before T2 and T3. Exercise at 3500 m (T2 and T3) via hypobaric hypoxia consisted of a 5-min warm-up (25% of normobaric VO2max) and four 5-min cycling bouts (40, 50, 60, 70% of normobaric VO2max) each separated by a 4-min rest period. Cycling RPM and watts for each submaximal bout during T2 and T3 were determined during T1. Preexercise plasma nitrite was elevated following NR consumption compared with PL (1.4 ± 1.2 and 0.7 ± 0.3 uM respectively; p < .05). There was no difference in oxygen consumption (-0.5 ± 1.8, 0.1 ± 1.7, 0.7 ± 2.1, and 1.0 ± 3.0 ml/kg/min) at any intensity (40, 50, 60, 70% of VO2max, respectively) between NR and PL. Further, respiratory exchange ratio, oxygen saturation, heart rate and rating of perceived exertion were not different at any submaximal intensity between NR and PL either. Blood lactate, however, was reduced following NR consumption compared with PL at 40 and 60% of VO2max (p < .0.05). Our findings suggest that acute nitrate supplementation before exercise at 3500 m does not reduce oxygen cost but may reduce blood lactate accumulation at lower intensity workloads.

Nitrate-Containing Beetroot Juice Reduces Oxygen Consumption During Submaximal Exercise in Low but Not High Aerobically Fit Male Runners.

Purpose: to examine the effect of a 4-day NO3- loading protocol on the submaximal oxygen cost of both low fit and high fit participants at five different exercise intensities. Methods: participants were initially assigned to a placebo (PL; negligible NO3-) or inorganic nitrate-rich (NR; 6.2 mmol nitrate/day) group; double-blind, placebo-controlled, crossover. Participants completed three trials (T1, T2 and T3). T1 included a maximal aerobic capacity (VO2max) treadmill test. A 6-day washout, minimizing nitrate consumption, preceded T2. Each of the four days prior to T2 and T3, participants consumed either PL or NR; final dose 2.5 hours prior to exercise. A 14-day washout followed T2. T2 and T3 consisted of 5-minute submaximal treadmill bouts (45, 60, 70, 80 and 85% VO2max) determined during T1. Results: Low fit nitrate-supplemented participants consumed less oxygen (p<0.05) at lower workloads (45% and 60% VO2max) compared to placebo trials; changes not observed in high fit participants. The two lowest intensity workloads of 45 and 60% VO2max revealed the greatest correlation (r=0.54, p=0.09 and r=0.79, p<0.05; respectively). No differences were found between conditions for heart rate, respiratory exchange ratio or rating of perceived exertion for either fitness group. Conclusion: Nitrate consumption promotes reduced oxygen consumption at lower exercise intensities in low fit, but not high fit males. Lesser fit individuals may receive greater benefit than higher fit participants exercising at intensities <60% VO2max.