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1.
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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2.
Nitrate Respiration in Thermus thermophilus NAR1: from Horizontal Gene Transfer to Internal Evolution.
Sánchez-Costa, M, Blesa, A, Berenguer, J
Genes. 2020;(11)
Abstract
Genes coding for enzymes of the denitrification pathway appear randomly distributed among isolates of the ancestral genus Thermus, but only in few strains of the species Thermus thermophilus has the pathway been studied to a certain detail. Here, we review the enzymes involved in this pathway present in T. thermophilus NAR1, a strain extensively employed as a model for nitrate respiration, in the light of its full sequence recently assembled through a combination of PacBio and Illumina technologies in order to counteract the systematic errors introduced by the former technique. The genome of this strain is divided in four replicons, a chromosome of 2,021,843 bp, two megaplasmids of 370,865 and 77,135 bp and a small plasmid of 9799 pb. Nitrate respiration is encoded in the largest megaplasmid, pTTHNP4, within a region that includes operons for O2 and nitrate sensory systems, a nitrate reductase, nitrate and nitrite transporters and a nitrate specific NADH dehydrogenase, in addition to multiple insertion sequences (IS), suggesting its mobility-prone nature. Despite nitrite is the final product of nitrate respiration in this strain, the megaplasmid encodes two putative nitrite reductases of the cd1 and Cu-containing types, apparently inactivated by IS. No nitric oxide reductase genes have been found within this region, although the NorR sensory gene, needed for its expression, is found near the inactive nitrite respiration system. These data clearly support that partial denitrification in this strain is the consequence of recent deletions and IS insertions in genes involved in nitrite respiration. Based on these data, the capability of this strain to transfer or acquire denitrification clusters by horizontal gene transfer is discussed.
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3.
Urinary nitrate concentration as a marker for kidney transplant rejection.
Riddell, A, Kirkwood, J, Smallwood, M, Winyard, P, Knight, B, Romanczuk, L, Shore, A, Gilchrist, M
BMC nephrology. 2020;(1):441
Abstract
BACKGROUND Early identification and treatment of kidney transplant rejection episodes is vital to limit loss of function and prolong the life of the transplanted kidney and recipient. Current practice depends on detecting a creatinine rise. A biomarker to diagnose transplant rejection at an earlier time point than current practice, or to inform earlier decision making to biopsy, could be transformative. It has previously been shown that urinary nitrate concentration is elevated in renal transplant rejection. Nitrate is a nitric oxide (NO) oxidation product. Transplant rejection upregulates NO synthesis via inducible nitric oxide synthase leading to elevations in urinary nitrate concentration. We have recently validated a urinary nitrate concentration assay which could provide results in a clinically relevant timeframe. Our aim was to determine whether urinary nitrate concentration is a useful tool to predict renal transplant rejection in the context of contemporary clinical practice. METHODS We conducted a prospective observational study, recruiting renal transplant participants over an 18-month period. We made no alterations to the patients' clinical care including medications, immunosuppression, diet and frequency of visits. We collected urine samples from every clinical attendance. We assessed the urinary nitrate to creatinine ratio (uNCR) between patient groups: routine attendances, biopsy proven rejection, biopsy proven no rejection and other call backs. uNCR was examined over time for those with biopsy proven transplant rejection. These four groups were compared using an ANOVA test. RESULTS A total of 2656 samples were collected. uNCR during biopsy proven rejection, n = 15 (median 49 μmol/mmol, IQR 23-61) was not significantly different from that of routine samples, n = 164 (median 55 μmol/mmol, IQR 37-82) (p = 0.55), or biopsy proven no rejection, n = 12 (median 39 μmol/mmol, IQR 21-89) (P = 0.77). Overall uNCR was highly variable with no diagnostic threshold for kidney transplant rejection. Furthermore, within-patient uNCR was highly variable over time, and thus it was not possible to produce individualised patient thresholds to identify rejection. The total taking Tacrolimus was 204 patients, with no statistical difference between the uNCR of all those on Tacrolimus, against those not, p = 0.18. CONCLUSION The urinary nitrate to creatinine ratio is not a useful biomarker for renal transplant rejection.
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4.
A plant's diet, surviving in a variable nutrient environment.
Oldroyd, GED, Leyser, O
Science (New York, N.Y.). 2020;(6486)
Abstract
As primary producers, plants rely on a large aboveground surface area to collect carbon dioxide and sunlight and a large underground surface area to collect the water and mineral nutrients needed to support their growth and development. Accessibility of the essential nutrients nitrogen (N) and phosphorus (P) in the soil is affected by many factors that create a variable spatiotemporal landscape of their availability both at the local and global scale. Plants optimize uptake of the N and P available through modifications to their growth and development and engagement with microorganisms that facilitate their capture. The sensing of these nutrients, as well as the perception of overall nutrient status, shapes the plant's response to its nutrient environment, coordinating its development with microbial engagement to optimize N and P capture and regulate overall plant growth.
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Untangling the molecular mechanisms and functions of nitrate to improve nitrogen use efficiency.
Iqbal, A, Qiang, D, Alamzeb, M, Xiangru, W, Huiping, G, Hengheng, Z, Nianchang, P, Xiling, Z, Meizhen, S
Journal of the science of food and agriculture. 2020;(3):904-914
Abstract
A huge amount of nitrogenous fertilizer is used to increase crop production. This leads to an increase in the cost of production, and to human and environmental problems. It is therefore necessary to improve nitrogen use efficiency (NUE) and to design agronomic, biotechnological and breeding strategies for better fertilizer use. Nitrogen use efficiency relies primarily on how plants extract, uptake, transport, assimilate, and remobilize nitrogen. Many plants use nitrate as a preferred nitrogen source. It acts as a signaling molecule in the various important physiological processes required for growth and development. As nitrate is the main source of nitrogen in the soil, root nitrate transporters are important subjects for study. The latest reports have also discussed how nitrate transporter and assimilation genes can be used as molecular tools to improve NUE in crops. The purpose of this review is to describe the mechanisms and functions of nitrate as a specific factor that can be addressed to increase NUE. Improving factors such as nitrate uptake, transport, assimilation, and remobilization through activation by signaling, sensing, and regulatory processes will improve plant growth and NUE. © 2019 Society of Chemical Industry.
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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.
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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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8.
Effect of Beetroot Juice Supplementation on Mood, Perceived Exertion, and Performance During a 30-Second Wingate Test.
Jodra, P, Domínguez, R, Sánchez-Oliver, AJ, Veiga-Herreros, P, Bailey, SJ
International journal of sports physiology and performance. 2020;(2):243-248
Abstract
PURPOSE Dietary supplementation with inorganic nitrate (NO3-) can enhance high-intensity exercise performance by improving skeletal muscle contractility and metabolism, but the extent to which this might be linked to altered psychophysiological processes is presently unclear. The purpose of this study was to assess the effects of NO3--rich beetroot juice (BJ) supplementation on profile of mood states, ratings of perceived exertion (RPE), and performance in a 30-second Wingate cycle test. METHODS In a double-blind, randomized, cross-over study, 15 subjects completed 2 laboratory sessions after ingesting NO3--rich or NO3--depleted (placebo) BJ. Participants initially completed the profile of mood states questionnaire. Subsequently, participants completed a warm-up followed by a 30-second all-out Wingate cycling test. After the Wingate test, participants immediately indicated the RPE of their leg muscles (RPEmuscular), cardiovascular system (RPEcardio), and general RPE (RPEgeneral). RESULTS Compared with the placebo condition, supplementation with BJ increased peak power output (Wpeak) (+4.4%, 11.5 [0.7] vs 11.1 [1.0] W·kg-1; P = .039) and lowered the time taken to reach Wpeak (7.3 [0.9] vs 8.7 [1.5] s; P = .002) during the Wingate test. The profile of mood states score linked to tension was increased prior to the Wingate test (4.8 [3.0] vs 3.4 [2.4]; P = .040), and RPEmuscular was lowered immediately following the Wingate test (17.7 [1.6] vs 18.3 [1.0]; P = .031), after BJ compared with placebo ingestion. CONCLUSIONS Acute BJ supplementation improved pre-exercise tension, 30-second Wingate test performance, and lowered postexercise RPEmuscular.
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Influence of Nitrate Supplementation on Endurance Cyclic Sports Performance: A Systematic Review.
Lorenzo Calvo, J, Alorda-Capo, F, Pareja-Galeano, H, Jiménez, SL
Nutrients. 2020;(6)
Abstract
Endurance can be defined as the capacity to maintain one's velocity or power output for the longest possible time. Maintaining such activity can lead to the onset of fatigue. Dietary nitrate supplementation produces an ergogenic effect due to the improvement of mitochondrial oxygen efficiency through a reduction in the oxygen cost of exercise that increases vasodilation and blood flow to the skeletal muscle in recreationally active subjects. However, the effects of dietary nitrate supplementation on well-trained endurance athletes remain unclear; such supplementation could affect more performance areas. In the present study, a systematic review of the literature was conducted to clarify the use and effects of nitrate as a dietary supplement in endurance athletes trained in cyclic sports (repetitive movement sports). A systematic search was carried out following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines in the databases of SCOPUS, Web of Science (WOS), Medline (PubMed), and Sport Discus from 1 January 2010 to 30 November 2019. Twenty-seven studies were included in the study. The methodological quality of the articles was assessed using the McMaster Critical Review Form. Statistically significant ergogenic results were obtained in 8 (29.63%) of the 27 studies investigated, with significant results obtained for cardiorespiratory parameters and performance measures. Improvement in exercise tolerance was obtained, which could help with exhaustion over time, while the improvement in exercise economics was not as clear. Additionally, the dose necessary for this ergogenic effect seems to have a direct relationship with the physical condition of the athlete. The acute dose is around 6-12.4 mmol/day of nitrate administered 2-3 h before the activity, with the same amount given as a chronic dose over 6-15 days. Further studies are required to understand the factors that affect the potential ergogenic impacts of nitrate on athletic performance among endurance athletes.
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Nitrate in 2020: Thirty Years from Transport to Signaling Networks.
Vidal, EA, Alvarez, JM, Araus, V, Riveras, E, Brooks, MD, Krouk, G, Ruffel, S, Lejay, L, Crawford, NM, Coruzzi, GM, et al
The Plant cell. 2020;(7):2094-2119
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Abstract
Nitrogen (N) is an essential macronutrient for plants and a major limiting factor for plant growth and crop production. Nitrate is the main source of N available to plants in agricultural soils and in many natural environments. Sustaining agricultural productivity is of paramount importance in the current scenario of increasing world population, diversification of crop uses, and climate change. Plant productivity for major crops around the world, however, is still supported by excess application of N-rich fertilizers with detrimental economic and environmental impacts. Thus, understanding how plants regulate nitrate uptake and metabolism is key for developing new crops with enhanced N use efficiency and to cope with future world food demands. The study of plant responses to nitrate has gained considerable interest over the last 30 years. This review provides an overview of key findings in nitrate research, spanning biochemistry, molecular genetics, genomics, and systems biology. We discuss how we have reached our current view of nitrate transport, local and systemic nitrate sensing/signaling, and the regulatory networks underlying nitrate-controlled outputs in plants. We hope this summary will serve not only as a timeline and information repository but also as a baseline to define outstanding questions for future research.