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Feasibility and acceptability of a nutritional intervention testing the effects of nitrate-rich beetroot juice and folic acid on blood pressure in Tanzanian adults with elevated blood pressure.
Kandhari, N, Prabhakar, M, Shannon, O, Fostier, W, Koehl, C, Rogathi, J, Temu, G, Stephan, BCM, Gray, WK, Haule, I, et al
International journal of food sciences and nutrition. 2021;(2):195-207
Abstract
Sub-Saharan African countries are experiencing an alarming increase in hypertension prevalence. This study evaluated the feasibility and acceptability of nitrate-rich beetroot and folate supplementation, alone or combined, for the reduction of blood pressure (BP) in Tanzanian adults with elevated BP. This was a three-arm double-blind, placebo-controlled, parallel randomised clinical trial. Forty-eight participants were randomised to one of three groups to follow a specific 60-day intervention which included a: (1) combined intervention (beetroot juice + folate), (2) single intervention (beetroot juice + placebo), and (3) control group (nitrate-depleted beetroot juice + placebo). Forty-seven participants (age: 50-70 years) completed the study. The acceptability of the interventions was high. Self-reported compliance to the interventions was more than 90% which was confirmed by the significant increase in nitrate and folate concentrations in plasma and saliva samples in the treatment arms. This study provides important information for the design of high-nitrate interventions to reduce BP in Sub-Saharan African countries.
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Body mass-normalized moderate dose of dietary nitrate intake improves endothelial function and walking capacity in patients with peripheral artery disease.
Pekas, EJ, Wooden, TK, Yadav, SK, Park, SY
American journal of physiology. Regulatory, integrative and comparative physiology. 2021;(2):R162-R173
Abstract
Peripheral artery disease (PAD) is characterized by the accumulation of atherosclerotic plaques in the lower extremity conduit arteries, which impairs blood flow and walking capacity. Dietary nitrate has been used to reduce blood pressure (BP) and improve walking capacity in PAD. However, a standardized dose for PAD has not been determined. Therefore, we sought to determine the effects of a body mass-normalized moderate dose of nitrate (0.11 mmol nitrate/kg) as beetroot juice on serum nitrate/nitrite, vascular function, walking capacity, and tissue oxygen utilization capacity in patients with PAD. A total of 11 patients with PAD received either nitrate supplement or placebo in a randomized crossover design. Total serum nitrate/nitrite, resting BP, brachial and popliteal artery endothelial function (flow-mediated dilation, FMD), arterial stiffness (pulse-wave velocity, PWV), augmentation index (AIx), maximal walking distance and time, claudication onset time, and skeletal muscle oxygen utilization were measured pre- and postnitrate and placebo intake. There were significant group × time interactions (P < 0.05) for serum nitrate/nitrite, FMD, BP, walking distance and time, and skeletal muscle oxygen utilization. The nitrate group showed significantly increased serum nitrate/nitrite (Δ1.32 μM), increased brachial and popliteal FMD (Δ1.3% and Δ1.7%, respectively), reduced peripheral and central systolic BP (Δ-4.7 mmHg and Δ-8.2 mmHg, respectively), increased maximal walking distance (Δ92.7 m) and time (Δ56.3 s), and reduced deoxygenated hemoglobin during walking. There were no changes in PWV, AIx, or claudication (P > 0.05). These results indicate that a body-mass normalized moderate dose of nitrate may be effective and safe for reducing BP, improving endothelial function, and improving walking capacity in patients with PAD.
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The effect of dietary nitrate on exercise capacity in chronic kidney disease: a randomized controlled pilot study.
Ramick, MG, Kirkman, DL, Stock, JM, Muth, BJ, Farquhar, WB, Chirinos, JA, Doulias, PT, Ischiropoulos, H, Edwards, DG
Nitric oxide : biology and chemistry. 2021;:17-23
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Abstract
BACKGROUND Chronic Kidney Disease (CKD) patients exhibit a reduced exercise capacity that impacts quality of life. Dietary nitrate supplementation has been shown to have favorable effects on exercise capacity in disease populations by reducing the oxygen cost of exercise. This study investigated whether dietary nitrates would acutely improve exercise capacity in CKD patients. METHODS AND RESULTS In this randomized, double-blinded crossover study, 12 Stage 3-4 CKD patients (Mean ± SEM: Age, 60 ± 5yrs; eGFR, 50.3 ± 4.6 ml/min/1.73 m2) received an acute dose of 12.6 mmol of dietary nitrate in the form of concentrated beetroot juice (BRJ) and a nitrate depleted placebo (PLA). Skeletal muscle mitochondrial oxidative function was assessed using near-infrared spectroscopy. Cardiopulmonary exercise testing was performed on a cycle ergometer, with intensity increased by 25 W every 3 min until volitional fatigue. Plasma nitric oxide (NO) metabolites (NOm; nitrate, nitrite, low molecular weight S-nitrosothiols, and metal bound NO) were determined by gas-phase chemiluminescence. Plasma NOm values were significantly increased following BRJ (BRJ vs. PLA: 1074.4 ± 120.4 μM vs. 28.4 ± 6.6 μM, p < 0.001). Total work performed (44.4 ± 10.6 vs 39.6 ± 9.9 kJ, p = 0.03) and total exercise time (674 ± 85 vs 627 ± 86s, p = 0.04) were significantly greater following BRJ. Oxygen consumption at the ventilatory threshold was also improved by BRJ (0.90 ± 0.08 vs. 0.74 ± 0.06 L/min, p = 0.04). These changes occurred in the absence of improved skeletal muscle mitochondrial oxidative capacity (p = 0.52) and VO2peak (p = 0.35). CONCLUSIONS Our findings demonstrate that inorganic nitrate can acutely improve exercise capacity in CKD patients. The effects of chronic nitrate supplementation on CKD related exercise intolerance should be investigated in future studies.
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Effect of hypoxia and nitrate supplementation on different high-intensity interval-training sessions.
Sousa, A, Viana, JL, Milheiro, J, Reis, VM, Millet, GP
European journal of applied physiology. 2021;(9):2585-2594
Abstract
PURPOSE To test the hypothesis that interval-training (IHT) would be impaired by hypoxia to a larger extent than repeated-sprint training (RSH) and that dietary nitrate (NO3-) would mitigate the detrimental effect of hypoxia to a larger extent during IHT than RSH. METHODS Thirty endurance-trained male participants performed IHT (6 × 1 min at 90%∆ with 1 min active recovery) and RSH (2 sets of 6 × 10 s "all-out" efforts with 20 s active recovery) on a cycle ergometer, allocated in one of three groups: normobaric hypoxia (~ 13% FiO2) + NO3- - HNO, n = 10; normobaric hypoxia + placebo - HPL, n = 10; normoxia (20.9% FiO2) + placebo - CON, n = 10. Submaximal oxygen uptake ([Formula: see text]O2), time spent above 90% of maximal [Formula: see text]O2 (≥ 90 [Formula: see text]O2max) and heart rate (≥ 90 HRmax) were compared between IHT and RSH sessions and groups. Additionally, mean power output (MPO), decrement score and % of power associated with [Formula: see text]O2max (%p[Formula: see text]O2max) in RSH sessions were analyzed. RESULTS [Formula: see text]O2 at sub-maximal intensities did not differ between training protocols and groups (~ 27 ml kg-1 min-1). ≥ 90 HRmax was significantly higher in IHT compared to RSH session (39 ± 8 vs. 30 ± 8%, p = 0.03) but only in HNO group. MPO (range 360-490 W) and decrement score (10-13%) were similar between groups although %p[Formula: see text]O2max was significantly higher (p = 0.04) in CON (166 ± 16 W) compared with both HPL (147 ± 15 W) and HNO (144 ± 10 W) groups. CONCLUSION IHT responses were neither more impaired by hypoxia than RSH ones. Moreover, dietary NO3- supplementation impacted equally IHT and RSH training responses' differences between hypoxia and normoxia.
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Acute supplementation with beetroot juice improves endothelial function in HIV-infected individuals.
Nogueira Soares, R, Machado-Santos, AP, Barros-Santos, E, Vieira De Oliveira, G, Murias, JM, Alvares, TS
Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme. 2021;(3):213-220
Abstract
Human immunodeficiency virus (HIV) is associated with lower nitric oxide (NO) bioavailability and vascular dysfunction. Nitrate-rich beetroot juice (BJ) has been shown to acutely increase NO availability and vascular function in healthy and individuals at high risk for cardiovascular disease. Thus, we tested the effects of BJ ingestion on flow-mediated dilation (FMD) and pulse wave velocity (PWV) measurements in healthy and HIV-infected patients. Thirteen HIV-infected individuals (age, 36 ± 10 years) and 18 healthy (age, 27 ± 8 years) participated in the study. Individuals were submitted to vascular tests such as FMD and pulse PWV at pre (T0) and at 120 min (T120) after BJ and placebo (PLA) ingestion. The %FMD at T0 of the control group was significantly higher than the %FMD at T0 of the HIV individuals in both interventions. BJ improved the %FMD at T120 when compared with T0 in the HIV and control groups. There was no change in %FMD after PLA ingestion in the control and HIV groups. There were no differences between groups (control vs HIV), time points (T0 vs T120), and interventions (BJ vs PLA) for PWV. Our findings showed that nitrate-rich BJ ingestion acutely improved vascular function in healthy and HIV-infected patients. Clinical Trials Registry no. NCT03485248. Novelty: HIV is associated with lower NO bioavailability and vascular dysfunction. Acute supplementation with nitrate-rich BJ has been shown to acutely increases NO bioavailability. We showed for the first time that BJ acutely improves endothelial function in HIV-infected patients.
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Oxidative stress and nitrate/nitrite (NOx) status following citrulline supplementation in type 2 diabetes: a randomised, double-blind, placebo-controlled trial.
Azizi, S, Ebrahimi-Mameghani, M, Mobasseri, M, Karamzad, N, Mahdavi, R
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2021;(1):64-72
Abstract
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.
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Dose-Response Effect of Dietary Nitrate on Muscle Contractility and Blood Pressure in Older Subjects: A Pilot Study.
Gallardo, EJ, Gray, DA, Hoffman, RL, Yates, BA, Moorthi, RN, Coggan, AR
The journals of gerontology. Series A, Biological sciences and medical sciences. 2021;(4):591-598
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Abstract
We have recently demonstrated that dietary nitrate, a source of nitric oxide (NO) via the nitrate → nitrite → NO enterosalivary pathway, can improve muscle contractility in healthy older men and women. Nitrate ingestion has also been shown to reduce blood pressure in some, but not all, studies of older individuals. However, the optimal dose for eliciting these beneficial effects is unknown. A pilot randomized, double-blind, placebo-controlled crossover study was therefore performed to determine the effects of ingesting 3.3 mL/kg of concentrated beetroot juice containing 0, 200, or 400 µmol/kg of nitrate in 9 healthy older subjects (mean age 70 ± 1 years). Maximal knee extensor power (Pmax) and speed (Vmax) were measured ~2.5 hours after nitrate ingestion using isokinetic dynamometry. Blood pressure was monitored periodically throughout each study. Pmax (in W/kg) was higher (p < .05) after the lower dose (3.9 ± 0.4) compared to the placebo (3.7 ± 0.4) or higher dose (3.7 ± 0.4). Vmax (in rad/s) also tended to be higher (p = .08) after the lower dose (11.9 ± 0.7) compared to the placebo (10.8 ± 0.8) or higher dose (11.2 ± 0.8). Eight out of 9 subjects achieved a higher Pmax and Vmax after the lower versus the higher dose. These dose-related changes in muscle contractility generally paralleled changes in breath NO levels. No significant changes were found in systolic, diastolic, or mean arterial blood pressure. A lower dose of nitrate increases muscle speed and power in healthy older individuals, but these improvements are lost at a higher dose. Blood pressure, on the other hand, is not reduced even with a higher dose.
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Oral nitrate supplementation to enhance pulmonary rehabilitation in COPD: ON-EPIC a multicentre, double-blind, placebo-controlled, randomised parallel group study.
Pavitt, MJ, Tanner, RJ, Lewis, A, Buttery, S, Mehta, B, Jefford, H, Curtis, KJ, Banya, WAS, Husain, S, Satkunam, K, et al
Thorax. 2020;(7):547-555
Abstract
RATIONALE Dietary nitrate supplementation has been proposed as a strategy to improve exercise performance, both in healthy individuals and in people with COPD. We aimed to assess whether it could enhance the effect of pulmonary rehabilitation (PR) in COPD. METHODS This double-blind, placebo-controlled, parallel group, randomised controlled study performed at four UK centres, enrolled adults with Global Initiative for Chronic Obstructive Lung Disease grade II-IV COPD and Medical Research Council dyspnoea score 3-5 or functional limitation to undertake a twice weekly 8-week PR programme. They were randomly assigned (1:1) to either 140 mL of nitrate-rich beetroot juice (BRJ) (12.9 mmol nitrate), or placebo nitrate-deplete BRJ, consumed 3 hours prior to undertaking each PR session. Allocation used computer-generated block randomisation. MEASUREMENTS The primary outcome was change in incremental shuttle walk test (ISWT) distance. Secondary outcomes included quality of life, physical activity level, endothelial function via flow-mediated dilatation, fat-free mass index and blood pressure parameters. RESULTS 165 participants were recruited, 78 randomised to nitrate-rich BRJ and 87 randomised to placebo. Exercise capacity increased more with active treatment (n=57) than placebo (n=65); median (IQR) change in ISWT distance +60 m (10, 85) vs +30 m (0, 70), estimated treatment effect 30 m (95% CI 10 to 40); p=0.027. Active treatment also impacted on systolic blood pressure: treatment group -5.0 mm Hg (-5.0, -3.0) versus control +6.0 mm Hg (-1.0, 15.5), estimated treatment effect -7 mm Hg (95% CI 7 to -20) (p<0.0005). No significant serious adverse events or side effects were reported. CONCLUSIONS Dietary nitrate supplementation appears to be a well-tolerated and effective strategy to augment the benefits of PR in COPD. TRIAL REGISTRATION NUMBER ISRCTN27860457.
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Dietary nitrate does not acutely enhance skeletal muscle blood flow and vasodilation in the lower limbs of older adults during single-limb exercise.
Hughes, WE, Kruse, NT, Ueda, K, Feider, AJ, Hanada, S, Bock, JM, Casey, DP
European journal of applied physiology. 2020;(6):1357-1369
Abstract
PURPOSE Blood flow (BF) and vasodilator responses to knee-extension exercise are attenuated in older adults across an exercise transient (onset, kinetics, and steady-state), and reduced nitric oxide bioavailability (NO) has been hypothesized to be a primary mechanism contributing to this attenuation. We tested the hypothesis acute dietary nitrate (NO3-) supplementation (~ 4.03 mmol NO3- and 0.29 mmol NO2-) would improve leg vasodilator responses across an exercise transient during lower limb exercise in older adults. METHODS Older (n = 10) untrained adults performed single and rhythmic knee-extension contractions at 20% and 40% work-rate maximum (WRmax) prior to and 2-h after consuming a NO3- or placebo beverage in a double-blind, randomized fashion. Femoral artery BF was measured by Doppler ultrasound. Vascular conductance was calculated using BF and mean arterial pressure. RESULTS Acute ingestion of dietary NO3- enhanced plasma [NO3-] and [NO2-] (P < 0.05). Neither dietary NO3- or placebo enhanced vasodilator responses at the onset of exercise or during steady state at 20% and 40% WRmax (P > 0.05). Leg vasodilator kinetics during rhythmic exercise remained unchanged following NO3- and placebo ingestion (P > 0.05). CONCLUSIONS The key findings of this study are that despite increasing plasma [NO3-] and [NO2-], acute dietary NO3- intake had no effect on (1) rapid hyperaemic or vasodilator responses at the onset of exercise; (2) hyperaemic and vasodilator responses during steady-state submaximal exercise; or (3) kinetics of vasodilation preceding steady-state responses. Collectively, these findings suggest that low dose dietary NO3- supplementation does not improve hyperaemic and vasodilator responses across an exercise transient in older adults.
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High dose Nitrate ingestion does not improve 40 km cycling time trial performance in trained cyclists.
Mosher, SL, Gough, LA, Deb, S, Saunders, B, Mc Naughton, LR, Brown, DR, Sparks, SA
Research in sports medicine (Print). 2020;(1):138-146
Abstract
This study evaluated the chronic effects of nitrate (NO3-) ingestion over three days, on 40 km TT performance in 11trained cyclists (VO2max: 60.8 ± 7.4 ml.kg-1.min-1; age: 36 ± 9 years; height: 1.80 ± 0.06 m; body mass: 87.2 ± 12.0 kg). Utilising a double-blind randomised cross-over design, participants completed three 40 km TT on a Velotron® ergometer following the ingestion of either a 140 ml of "BEET It sport®" NO3- shot containing 12.8 mmol or 800 mg of NO3-, a placebo drink or nothing (control). Performance, oxygen consumption (VO2), blood bicarbonate (HCO3-), pH and lactate (BLa) and ratings of perceived exertion (RPE) were measured every 10 km throughout the TT. The present findings show that NO3- ingestion had no effect on TT performance (NO3-: 4098.0 ± 209.8 vs. Placebo: 4161.9 ± 263.3 s, p = 0.296, ES = 0.11), or VO2 (p = 0.253, ES = 0.13). Similarly, blood lactate and RPE were also unaffected by the experimental conditions (p = 0.522, ES = 0.06; p = 0.085, ES = 0.30) respectively. Therefore, these results suggest that a high dose of NO3- over three days has limited efficacy as an ergogenic aid for 40 km TT cycling performance in trained cyclists.