Physiological and performance effects of dietary nitrate and N-acetylcysteine supplementation during prolonged heavy-intensity cycling.

The purpose of this study was to investigate effects of concurrent and independent administration of dietary nitrate (NO3-), administered as NO3--rich beetroot juice (BR; ~12.4 mmol of NO3-), and N-acetylcysteine (NAC; 70 mg·kg-1) on physiological responses during prolonged exercise and subsequent high-intensity exercise tolerance. Sixteen recreationally active males supplemented with NO3--depleted beetroot juice (PL) or BR for 6 days and ingested an acute dose of NAC or maltodextrin (MAL) 1 h prior to performing 1 h of heavy-intensity cycling exercise immediately followed by a severe-intensity time-to-exhaustion (TTE) test in four conditions: 1) PL+MAL, 2) PL+NAC, 3) BR+MAL and 4) BR+NAC. Pre-exercise plasma [NO3-] and nitrite ([NO2-]) were elevated following BR+NAC  and BR+MAL (both P < 0.01) compared with PL+NAC and PL+MAL; plasma [cysteine] was increased in PL+NAC  and BR+NAC (both P < 0.01) compared to PL+MAL. Muscle excitability declined over time during the prolonged cycling bout in all conditions  but was better preserved in PL+NAC  compared to BR+NAC (P < 0.01) and PL+MAL (P < 0.05). There was no effect of supplementation on subsequent TTE . These findings indicate that co-ingestion of BR and NAC does not appreciably alter physiological responses during prolonged heavy-intensity cycling or enhance subsequent exercise tolerance.

High-Throughput Griess Assay of Nitrite and Nitrate in Plasma and Red Blood Cells for Human Physiology Studies under Extreme Conditions.

The metabolism of nitric oxide plays an increasingly interesting role in the physiological response of the human body to extreme environmental conditions, such as underwater, in an extremely cold climate, and at low oxygen concentrations. Field studies need the development of analytical methods to measure nitrite and nitrate in plasma and red blood cells with high requirements of accuracy, precision, and sensitivity. An optimized spectrophotometric Griess method for nitrite-nitrate affords sensitivity in the low millimolar range and precision within ±2 µM for both nitrite and nitrate, requiring 100 µL of scarcely available plasma sample or less than 50 µL of red blood cells. A scheduled time-efficient procedure affords measurement of as many as 80 blood samples, with combined nitrite and nitrate measurement in plasma and red blood cells. Performance and usefulness were tested in pilot studies that use blood fractions deriving from subjects who dwelt in an Antarctica scientific station and on breath-holding and scuba divers who performed training at sea and in a land-based deep pool facility. The method demonstrated adequate to measure low basal concentrations of nitrite and high production of nitrate as a consequence of water column pressure-triggered vasodilatation in deep-water divers.

Marching to the Beet: The effect of dietary nitrate supplementation on high altitude exercise performance and adaptation during a military trekking expedition.

PURPOSE: The aim was to investigate the effect of dietary nitrate supplementation (in the form of beetroot juice, BRJ) for 20 days on salivary nitrite (a potential precursor of bioactive nitric oxide), exercise performance and high altitude (HA) acclimatisation in field conditions (hypobaric hypoxia). METHODS: This was a single-blinded randomised control study of 22 healthy adult participants (12 men, 10 women, mean age 28 ± 12 years) across a HA military expedition. Participants were randomised pre-ascent to receive two 70 ml dose per day of either BRJ (~12.5 mmol nitrate per day; n = 11) or non-nitrate calorie matched control (n = 11). Participants ingested supplement doses daily, beginning 3 days prior to departure and continued until the highest sleeping altitude (4800 m) reached on day 17 of the expedition. Data were collected at baseline (44 m altitude), at 2350 m (day 9), 3400 m (day 12) and 4800 m (day 17). RESULTS: BRJ enhanced the salivary levels of nitrite (p = 0.007). There was a significant decrease in peripheral oxygen saturation and there were increases in heart rate, diastolic blood pressure, and rating of perceived exertion with increasing altitude (p=<0.001). Harvard Step Test fitness scores significantly declined at 4800 m in the control group (p = 0.003) compared with baseline. In contrast, there was no decline in fitness scores at 4800 m compared with baseline (p = 0.26) in the BRJ group. Heart rate recovery speed following exercise at 4800 m was significantly prolonged in the control group (p=<0.01) but was unchanged in the BRJ group (p = 0.61). BRJ did not affect the burden of HA illness (p = 1.00). CONCLUSIONS: BRJ increases salivary nitrite levels and ameliorates the decline in fitness at altitude but does not affect the occurrence of HA illness.

The effects of local versus systemic passive heating on the acute inflammatory, vascular and glycaemic response.

The aim of this study was to compare the acute cardiometabolic and perceptual responses between local and whole-body passive heating. Using a water-perfused suit, 10 recreationally active males underwent three 90 min conditions: heating of the legs with upper-body cooling (LBH), whole-body heating (WBH) and exposure to a thermoneutral temperature (CON). Blood samples were collected before and up to 3 h post-session to assess inflammatory markers, while a 2 h oral glucose tolerance test was initiated 1 h post-session. Femoral artery blood flow and perceptual responses were recorded at regular intervals. The interleukin (IL)-6 incremental area under the curve (iAUC) was higher for LBH (1096 ± 851 pg/mL × 270 min) and WBH (833 ± 476 pg/mL × 270 min) compared with CON (565 ± 325 pg/mL × 270 min; p < 0.047). Glucose concentrations were higher after WBH compared with LBH and CON (p < 0.046). Femoral artery blood flow was higher at the end of WBH (1713 ± 409 mL/min) compared with LBH (943 ± 349 mL/min; p < 0.001), and higher in LBH than CON (661 ± 222 mL/min; p = 0.002). Affect and thermal comfort were more negative during WBH compared with LBH and CON (p < 0.010). In conclusion, local passive heating elevated blood flow and the IL-6 iAUC. However, while resulting in more positive perceptual responses, the majority of the included cardiometabolic markers were attenuated compared with WBH. Novelty: The increase in the IL-6 iAUC in response to passive heating is not reduced by upper-body cooling. Upper-body cooling attenuates the plasma nitrite, IL-1ra and femoral artery blood flow response to passive heating. Upper-body cooling leads to more positive perceptual responses to passive heating.

Pharmacokinetics of Nitrate and Nitrite Following Beetroot Juice Drink Consumption.

BACKGROUND: Nitrate (NO3 -)-rich beetrAs BR juice can naturally contain both NO3 In four separate treatments, 11 healthy adults consumed 250 mL of BR containing one of the following: (i) high NO3 Ingestion of the HL and MM BR increased plasma [NO2 Inorganic NO3 - consumptio

No thermoregulatory or ergogenic effect of dietary nitrate among physically inactive males, exercising above gas exchange threshold in hot and dry conditions.

The aim of this study was to determine the effect of five days dietary nitrate (NO3-) consumption on exercise tolerance and thermoregulation during cycling in hot, dry conditions. In a double-blind, randomised crossover design, 11 healthy males participated in an exercise tolerance test (Tlim) in the heat (35°C, 28% relative humidity), cycling above the thermoneutral gas exchange threshold, after five days of dietary supplementation, with either NO3-rich beetroot juice (BR; ∼ 9.2 mmol NO3-) or placebo (PLA). Changes in plasma [NO3-] and nitrite [NO2-], core and mean skin temperatures, mean local and whole-body sweat rates, heart rate, perceptual ratings and pulmonary gas exchange were measured during exercise, alongside calorimetric estimations of thermal balance. Mean arterial pressures (MAP) were recorded pre-Tlim. There were no differences in Tlim between conditions (BR = 22.8 ± 8.1 min; Placebo = 20.7 ± 7.9 min) (P = 0.184), despite increases in plasma [NO3-] and [NO2-] (P < 0.001) and a 3.8% reduction in resting MAP (P = 0.004) in the BR condition. There were no other differences in thermoregulatory, cardio-metabolic, perceptual or calorimetric responses to the Tlim between conditions (P > 0.05). Dietary NO3- supplementation had no effect on exercise tolerance or thermoregulation in hot, dry conditions, despite reductions in resting MAP and increases in plasma [NO3-] and [NO2-]. Healthy, yet physically inactive individuals with no known impairments in vasodilatory and sudomotor function do not appear to require BR for ergogenic or thermolytic effects during exercise in the heat.

The impact of beetroot juice supplementation on muscular endurance, maximal strength and countermovement jump performance.

Purpose: Dietary nitrate has been shown to enhance muscle contractile function and has, therefore, been linked to increased muscle power and sprint exercise performance. However, the impact of dietary nitrate supplementation on maximal strength, performance and muscular endurance remains to be established. Methods: Fifteen recreationally active males (25 ± 4 y, BMI 24 ± 3 kg/m2) participated in a randomized double-blinded cross-over study comprising two 6-d supplementation periods; 140 mL/d nitrate-rich (BR; 985 mg/d) and nitrate-depleted (PLA; 0.37 mg/d) beetroot juice. Three hours following the last supplement, we assessed countermovement jump (CMJ) performance, maximal strength and power of the upper leg by voluntary isometric (30° and 60° angle) and isokinetic contractions (60, 120, 180 and 300°·s-1), and muscular endurance (total workload) by 30 reciprocal isokinetic voluntary contractions at 180°·s-1. Results: Despite differences in plasma nitrate (BR: 879 ± 239 vs. PLA: 33 ± 13 µmol/L, P < 0.001) and nitrite (BR: 463 ± 217 vs. PLA: 176 ± 50 nmol/L, P < 0.001) concentrations prior to exercise testing, CMJ height (BR: 39.3 ± 6.3 vs. PLA: 39.6 ± 6.3 cm; P = 0.39) and muscular endurance (BR: 3.93 ± 0.69 vs. PLA: 3.90 ± 0.66 kJ; P = 0.74) were not different between treatments. In line, isometric strength (P > 0.50 for both angles) and isokinetic knee extension power (P > 0.33 for all velocities) did not differ between treatments. Isokinetic knee flexion power was significantly higher following BR compared with PLA ingestion at 60°·s-1 (P = 0.001), but not at 120°·s-1 (P = 0.24), 180°·s-1 (P = 0.066), and 300°·s-1 (P = 0.36). Conclusion: Nitrate supplementation does not improve maximal strength, countermovement jump performance and muscular endurance in healthy, active males.

Oxidative stress and nitrate/nitrite (NOx) status following citrulline supplementation in type 2 diabetes: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The pathogenesis of diabetes is accompanied by oxidative stress. Citrulline can be considered as a potent antioxidant. The present study aimed to examine the effects of citrulline supplementation on the status of oxidative stress and serum levels of nitrite/nitrate (NOx) in patients suffering from type 2 diabetes (T2DM). METHODS: The present study comprises a double-blind placebo-controlled randomised clinical trial. The study subjects include 54 patients with T2DM chosen from specialised clinics of Tabriz University of Medical Sciences. The patients were allocated to one of the placebo or intervention groups. The patients in the placebo and the intervention group received one sachet of microcrystalline cellulose or l-citrulline (3 g), respectively, every day for 2 months. Malondialdehyde (MDA), glutathione peroxidase (GPx), total antioxidant capacity (TAC), superoxide dismutase (SOD), serum levels of fasting blood sugar (FBS), citrulline and NOx were assessed before and after the intervention. RESULTS: Forty-five patients completed the trial. Significant decreases were found in serum levels of FBS and MDA. Serum levels of TAC, citrulline and NOx in the intervention group increased compared to those of the placebo group, after adjusting the data for the baseline values and confounders. Differences between and within the two groups were statistically nonsignificant for GPx and SOD at the end of the study. Body mass index and energy intake were not changed significantly after the intervention. CONCLUSIONS: The results of the present study show the positive effects of citrulline supplementation with respect to attenuating FBS levels and oxidative stress, as well as boosting NOx status, in patients with T2DM.

Nitrate-rich beetroot juice offsets salivary acidity following carbohydrate ingestion before and after endurance exercise in healthy male runners.

There have been recent calls for strategies to improve oral health in athletes. High carbohydrate diets, exercise induced dehydration and transient perturbations to immune function combine to increase oral disease risk in this group. We tested whether a single dose of nitrate (NO3-) would offset the reduction in salivary pH following carbohydrate ingestion before and after an exercise bout designed to cause mild dehydration. Eleven trained male runners ([Formula: see text] 53 ± 9 ml∙kg-1∙min-1, age 30 ± 7 years) completed a randomised placebo-controlled study comprising four experimental trials. Participants ingested the following fluids one hour before each trial: (a) 140 ml of water (negative-control), (b) 140 ml of water (positive-control), (c) 140 ml of NO3- rich beetroot juice (~12.4 mmol NO3-) (NO3- trial) or (d) 140 ml NO3- depleted beetroot juice (placebo-trial). During the negative-control trial, participants ingested 795 ml of water in three equal aliquots: before, during, and after 90 min of submaximal running. In the other trials they received 795 ml of carbohydrate supplements in the same fashion. Venous blood was collected before and after the exercise bout and saliva was sampled before and repeatedly over the 20 min following carbohydrate or water ingestion. As expected, nitrite (NO2-) and NO3- were higher in plasma and saliva during the NO3- trial than all other trials (all P<0.001). Compared to the negative-control, salivary-pH was significantly reduced following the ingestion of carbohydrate in the positive-control and placebo trials (both P <0.05). Salivary-pH was similar between the negative-control and NO3- trials before and after exercise despite ingestion of carbohydrate in the NO3- trial (both P≥0.221). Ingesting NO3- attenuates the expected reduction in salivary-pH following carbohydrate supplements and exercise-induced dehydration. NO3- should be considered by athletes as a novel nutritional strategy to reduce the risk of developing acidity related oral health conditions.

The Effect of Dietary Inorganic Nitrate Supplementation on Cardiac Function during Submaximal Exercise in Men with Heart Failure with Reduced Ejection Fraction (HFrEF): A Pilot Study.

Heart failure with reduced ejection fraction (HFrEF) is a common end point for patients with coronary artery disease and it is characterized by exercise intolerance due, in part, to a reduction in cardiac output. Nitric oxide (NO) plays a vital role in cardiac function and patients with HFrEF have been identified as having reduced vascular NO. This pilot study aimed to investigate if nitrate supplementation could improve cardiac measures during acute, submaximal exercise. Five male participants (61 ± 3 years) with HFrEF (EF 32 ± 2.2%) completed this pilot study. All participants supplemented with inorganic nitrate (beetroot juice) or a nitrate-depleted placebo for ~13 days prior to testing. Participants completed a three-stage submaximal exercise protocol on a recumbent cycle ergometer with simultaneous echocardiography for calculation of cardiac output (Q), stroke volume (SV), and total peripheral resistance (TPR). Heart rate and blood pressure were measured at rest and during each stage. Both plasma nitrate (mean = ~1028%, p = 0.004) and nitrite (mean = ~109%, p = 0.01) increased following supplementation. There were no differences between interventions at rest, but the percent change in SV and Q from rest to stage two and stage three of exercise was higher following nitrate supplementation (all p > 0.05, ES > 0.8). Both interventions showed decreases in TPR during exercise, but the percent reduction TPR in stages two and three was greater following nitrate supplementation (p = 0.09, ES = 0.98 and p = 0.14, ES = 0.82, respectively). There were clinically relevant increases in cardiac function during exercise following supplementation with nitrate. The findings from this pilot study warrant further investigation in larger clinical trials.

A randomized controlled trial of nitrate supplementation in well-trained middle and older-aged adults.

PURPOSE: Nitrate (NO3-), through its conversion to nitrite (NO2-) and nitric oxide, has been shown to increase exercise tolerance in healthy younger adults and older diseased patients. Nitrate's effect in well-trained middle to older-aged adults has not been studied. Therefore, the purpose of this investigation was to examine the effects of a NO3- rich beverage on submaximal constant work rate exercise time in well-trained middle to older-aged adults. METHODS: This was a randomized controlled cross-over trial with 15 well-trained middle to older-aged adults, 41-64 year-old, who received one of two treatments (NO3- rich beverage then placebo or placebo then NO3- rich beverage), after which an exercise test at 75 percent of the subject's maximal work rate was completed. RESULTS: The NO3- rich beverage increased plasma NO3- and NO2- levels by 260 µM and 0.47 µM, respectively (p<0.001). Exercise time was not significantly different (p = 0.31) between the NO3- rich versus placebo conditions (1130±151 vs 1060±132 sec, respectively). Changes in exercise time between the two conditions ranged from a 55% improvement to a 40% decrease with the NO3- rich beverage. Oxygen consumption and rating of perceived exertion were not significantly different between the two conditions. CONCLUSION: In middle to older-aged well-trained adults, NO3- supplementation has non-significant, albeit highly variable, effects on exercise tolerance. ClinicalTrials.gov Identifier: NCT03371966.

Long-term nitric oxide synthase inhibition prevents 17ß-estradiol-induced suppression of cyclooxygenase-dependent contractions and enhancement of endothelium-dependent hyperpolarization-like relaxation in mesenteric arteries of ovariectomized rats.

Endothelial dysfunction is associated with a reduced bioavailability of nitric oxide (NO). In this study, the effects of 17ß-estradiol supplement on endothelial function were examined in ovariectomized (OVX) rats following long-term inhibition of NO synthases with L-NAME. Female Sprague Dawley rats were ovariectomized at 12 weeks old. They were supplemented with 17ß-estradiol (25 µg/kg/day, intramuscularly) or its vehicle (olive oil) until they were killed. At 18 weeks old, they were administered daily with NO synthase inhibitor L-NAME (60 mg/kg, by gavage) or its vehicle (distilled water) for 6 weeks. Rats were then anesthetized for blood pressure measurement and for isolation of mesenteric arteries and aortae for isometric tension measurement. Long-term L-NAME-treatment, without or with 17ß-estradiol supplement, resulted in reduced plasma nitrite/nitrate level without causing an increase in blood pressure in OVX rats. Acute inhibition of cyclooxygenase (COX) with indomethacin improved relaxations of mesenteric arteries to the calcium ionophore A23187 in OVX rats, and in those with long-term L-NAME-treatment without or with 17ß-estradiol supplement, but not in those with female hormone supplement only. 17ß-estradiol supplement or long-term L-NAME-treatment resulted in a greater endothelium-dependent hyperpolarization-like relaxation in mesenteric arteries. In the quiescent aorta, 17ß-estradiol supplement or long-term L-NAME-treatment unmasked the COX-dependent components of A23187-induced contractions, but prevented that of the smooth muscle contractions to U46619 in OVX rats. In summary, long-term 17ß-estradiol-supplement results in differential effects in different blood vessel types, and its beneficial vascular effects are masked under the conditions with NO synthase inhibition.

The effects of combined magnesium and zinc supplementation on metabolic status in patients with type 2 diabetes mellitus and coronary heart disease.

BACKGROUND: The present research aimed to analyze the impacts of magnesium and zinc supplements on glycemic control, serum lipids, and biomarkers of oxidative stress and inflammation in patients suffering from coronary heart disease (CHD) and type 2 diabetes mellitus (T2DM). METHODS: According to the research design, a randomized, double-blind, placebo-controlled trial has been implemented on 60 subjects suffering from CHD and T2DM. Therefore, participants have been randomly divided into 2 groups for taking placebo (n = 30) or 250 mg magnesium oxide plus 150 mg zinc sulfate (n = 30) for 12 weeks. RESULTS: Magnesium and zinc significantly decreased fasting plasma glucose (FPG) (ß - 9.44 mg/dL, 95% CI, - 18.30, - 0.57; P = 0.03) and insulin levels (ß - 1.37 µIU/mL, 95% CI, - 2.57, - 0.18; P = 0.02). Moreover, HDL-cholesterol levels significantly enhanced (ß 2.09 mg/dL, 95% CI, 0.05, 4.13; P = 0.04) in comparison to the placebo. There was an association between magnesium and zinc intake, and a significant decrease of C-reactive protein (CRP) (ß - 0.85 mg/L, 95% CI, - 1.26, - 0.45; P < 0.001), a significant increase in total nitrite (ß 5.13 µmol/L, 95% CI, 1.85, 8.41; P = 0.003) and total antioxidant capacity (TAC) (ß 43.44 mmol/L, 95% CI, 3.39, 83.50; P = 0.03) when compared with placebo. Furthermore, magnesium and zinc significantly reduced the Beck Depression Inventory index (BDI) (ß - 1.66; 95% CI, - 3.32, - 0.009; P = 0.04) and Beck Anxiety Inventory (BAI) (ß - 1.30; 95% CI, - 2.43, - 0.16; P = 0.02) when compared with the placebo. CONCLUSIONS: In patients with T2DM and CHD, the 12-week intake of magnesium plus zinc had beneficial effects on FPG, HDL-cholesterol, CRP, insulin, total nitrite, TAC levels, and BDI and BAI score. This suggests that magnesium and zinc co-supplementation may be beneficial for patients with T2DM and CHD. Further studies on more patients and lasting longer are needed to determine the safety of magnesium and zinc co-supplementation. TRIAL REGISTRATION: Current Controlled Trials http://www.irct.ir: IRCT20130211012438N31 at 11 May 2019 of registration. This study retrospectively registered.

A Nitrate-Rich Vegetable Intervention Elevates Plasma Nitrate and Nitrite Concentrations and Reduces Blood Pressure in Healthy Young Adults.

BACKGROUND: Emerging evidence suggests that increasing dietary nitrate intake may be an effective approach to reduce blood pressure. Beetroot juice is often used to supplement dietary nitrate, whereas nitrate intake levels from habitual diet are low. An increase in the habitual intake of nitrate-rich vegetables may represent an alternative to nitrate supplementation. However, the effectiveness and acceptability of a nitrate-rich-vegetables diet remain to be established. OBJECTIVE: The aim was to investigate the effect and feasibility of two different intervention strategies to increase dietary nitrate intake, on plasma nitrate/nitrite concentrations and blood pressure. DESIGN: A randomized, crossover trial was used. PARTICIPANTS: Participants were healthy men and women (both n=15; age: 24±6 years) from the Netherlands. INTERVENTION: Participants were instructed to consume ∼400 mg nitrate at lunch, provided through nitrate-rich vegetables and dietary counseling, or beetroot juice supplementation. Both interventions lasted 1 week, with 1-week washout (January to April 2017). MAIN OUTCOME: Plasma nitrate and nitrite concentrations and resting systolic and diastolic blood pressure were measured in an overnight fasted state (before and after intervention) and ∼2.5 hours after lunch (before and throughout intervention on day 1, 4, and 7). STATISTICAL ANALYSIS: Two-factor (time × treatment) repeated-measures analyses of variance were performed. RESULTS: Mean plasma nitrate concentrations increased with both interventions, with a larger increase in beetroot juice vs nitrate-rich vegetables, both in a fasted state and ∼2.5 hours after lunch (day 1, beetroot juice: 2.31±0.56 mg/dL [373±90 µmol/L] vs nitrate-rich vegetables: 1.71±0.83 mg/dL [277±134 µmol/L]; P<0.001). Likewise, mean plasma nitrite concentrations increased with both interventions, but were higher after lunch in beetroot juice than in nitrate-rich vegetables (day 1: 2.58±1.52 µg/dL [560±331 nmol/L] vs 2.15±1.21 µg/dL [468±263 nmol/L]; P=0.020). Fasting mean systolic and diastolic blood pressure did not change, but mean systolic and diastolic blood pressure assessed ∼2.5 hours after lunch were significantly reduced throughout both intervention periods (P<0.05), with no differences between beetroot juice and nitrate-rich vegetables (day 1, systolic blood pressure: -5.1±9.5 mm Hg and diastolic blood pressure: -5.3±8.9 mm Hg). CONCLUSION: Short-term consumption of dietary nitrate in the form of nitrate-rich vegetables represents an effective means to increase plasma nitrate and nitrite concentrations, and reduces blood pressure to the same extent as beetroot juice supplementation.

Antihypertensive effect of Phragmanthera incana (Schum) Balle on NG-nitro-L-Arginine methyl ester (L-NAME) induced hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Phragmanthera incana (Schum) Balle is a member of the African mistletoes that has been reported to be used in ethnomedicine for the treatment of hypertension. AIM: The aim of this study was to investigate the antihypertensive effect of Phragmanthera incana leaf ethanol extract (PILEE) in NG-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats. MATERIALS AND METHODS: Phytochemical analysis of PILEE was determined using the Gas chromatography - Mass spectrophotometry (GC-MS) method. Antihypertensive activity was investigated in rats that received PILEE (50, 100 and 200 mg/kg) or captopril (40 mg/kg) daily for 28 days together with oral administration of L-NAME (40 mg/kg). Blood pressure parameters were measured on day 7, 14, 21 and 28. Blood was obtained for determination of serum nitrite, interleukin-6 (IL-6) and tumor necrosis factor, TNF-α. The heart, liver and kidneys were used to determine oxidative stress indices (malondialdehyde, reduced glutathione and catalase). The cardiac tissue was processed for histopathological changes. RESULTS: The GC-MS profiling of PILEE identified 20 compounds namely fatty acid esters. Administration of PILEE (50, 100 and 200 mg/kg) dose dependently and significantly reduced systolic blood pressure and mean arterial pressure in hypertensive rats. PILEE administration significantly (p < 0.05) reversed elevated IL-6 and TNF-α in hypertensive rats. PILEE demonstrated antioxidant activity by attenuating L-NAME-induced elevated malondialdehyde and depletion of reduced glutathione and catalase activity in rat tissues. PILEE treatment demonstrated cardioprotective effect in L-NAME-induced cardiac hyperplasia and necrosis in rats. CONCLUSION: It can be concluded that Phragmanthera incana leaf ethanol extract possess antihypertensive, antioxidant and anti-inflammatory properties, suggesting a protective role in cardiovascular diseases.

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.

Influence of muscle oxygenation and nitrate-rich beetroot juice supplementation on O2 uptake kinetics and exercise tolerance.

We tested the hypothesis that acute supplementation with nitrate (NO3-)-rich beetroot juice (BR) would improve quadriceps muscle oxygenation, pulmonary oxygen uptake (V˙O2) kinetics and exercise tolerance (Tlim) in normoxia and that these improvements would be augmented in hypoxia and attenuated in hyperoxia. In a randomised, double-blind, cross-over study, ten healthy males completed two-step cycle tests to Tlim following acute consumption of 210 mL BR (18.6 mmol NO3-) or NO3--depleted beetroot juice placebo (PL; 0.12 mmol NO3-). These tests were completed in normobaric normoxia [fraction of inspired oxygen (FIO2): 21%], hypoxia (FIO2: 15%) and hyperoxia (FIO2: 40%). Pulmonary V˙O2 and quadriceps tissue oxygenation index (TOI), derived from multi-channel near-infrared spectroscopy, were measured during all trials. Plasma [nitrite] was higher in all BR compared to all PL trials (P < 0.05). Quadriceps TOI was higher in normoxia compared to hypoxia (P < 0.05) and higher in hyperoxia compared to hypoxia and normoxia (P < 0.05). Tlim was improved after BR compared to PL ingestion in the hypoxic trials (250 ± 44 vs. 231 ± 41 s; P = 0.006; d = 1.13), with the magnitude of improvement being negatively correlated with quadriceps TOI at Tlim (r = -0.78; P < 0.05). Tlim was not improved following BR ingestion in normoxia (BR: 364 ± 98 vs. PL: 344 ± 78 s; P = 0.087, d = 0.61) or hyperoxia (BR: 492 ± 212 vs. PL: 472 ± 196 s; P = 0.273, d = 0.37). BR ingestion increased peak V˙O2 in hypoxia (P < 0.05), but not normoxia or hyperoxia (P > 0.05). These findings indicate that BR supplementation is more likely to improve Tlim and peak V˙O2 in situations when skeletal muscle is more hypoxic.

Effects of photobiomodulation on interleukin-10 and nitrites in individuals with relapsing-remitting multiple sclerosis - Randomized clinical trial.

OBJECTIVE: Investigate the effects of photobiomodulation (PBM) on the expression of IL-10 and nitrites in individuals with Relapsing-Remitting multiple sclerosis (MS), as these biomarkers play a fundamental role in the physiopathology of the disease. The modulation of IL-10 and nitrites through treatment with PBM may be a novel treatment modality for MS. METHODS: A randomized, uncontrolled, clinical trial was conducted involving 14 individuals with a diagnosis of Relapsing-Remitting MS and a score of up to 6.0 on the Expanded Disability Status Scale (EDSS). THE PARTICIPANTS WERE RANDOMIZED TO TWO GROUPS: Group 1 -PBM in the sublingual region; Group 2 -PBM over the radial artery. Irradiation was administered with a wavelength of 808 nm and output power of 100 mW for 360 seconds twice a week, totaling 24 sessions. Peripheral blood was analyzed for the determination of serum levels of IL-10 and nitrites. RESULTS: After treatment with PBM, the expression of IL-10 increased in both the sublingual group (pre-treatment: 2.8 ± 1.4 pg/ml; post-treatment: 8.3 ± 2.4 pg/ml) and the radial artery group (pre-treatment: 2.7 pg/ml ± 1.4; post-treatment: 11.7 ± 3.8 pg/ml). In contrast, nitrite levels were not modulated in the sublingual group (pre-treatment: 65 ± 50 nmol/mg protein; post-treatment: 51 ± 42 nmol/mg protein) or the radial artery group (pre-treatment: 51 ± 16 nmol/mg protein; post-treatment: 42 ± 7 nmol/mg protein). CONCLUSION: Treatment with PBM positively modulated the expression of IL-10 but had no effect on nitrite levels. Further studies should be conducted with a larger sample and a control group, as PBM may be a promising complementary treatment for the management of MS. This trial is registered at ClinicalTrials.gov. Identifier: NCT03360487.