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The Efficacy of Nitrates for Bone Health: A Systematic Review and Meta-Analysis of Observational and Randomized Controlled Studies.
Liu, W, Meng, Z, Wang, G
Frontiers in endocrinology. 2022;:833932
Abstract
BACKGROUND Although some studies have found that nitrates were beneficial for bone health, the findings are inconsistent. To assess the efficacy of nitrates for bone health, we conducted a meta-analysis. METHODS PubMed, EMBASE databases, Cochrane Library for relevant articles published before December 2021 were searched. All observational and randomized controlled studies that reporting bone mineral density (BMD), fractures with nitrates use were included. A meta-analysis was performed to calculate risk ratios (RRs) for fractures, change differences for bone mineral density. RESULTS Four cohort studies and two case-control studies examining the association between nitrates use and fractures were identified. The nitrates use was not associated with any fracture risk (RR = 0.97; 95% CI, 0.94-1.01; I2 = 31.5%) and hip fracture (RR = 0.88; 95% CI, 0.76-1.02; I2 = 74.5%). Subgroup analyses revealed no differences in fracture risk, whereas two cohort studies revealed a reduced risk of hip fracture (RR = 0.71, 95% CI, 0.58-0.86, I2 = 0.0%). There were no statistically significant differences in BMD percent changes at lumbar spine (WMD = -0.07, 95% CI,-0.78-0.65; I2 = 0.0%), total hip (WMD = -0.42, 95% CI,-0.88-0.04; I2 = 0.0%), femoral neck (WMD = -0.38, 95% CI,-1.02-0.25; I2 = 0.0%), or total body (WMD = -0.17, 95% CI,-0.51-0.17; I2 = 0.0%) in two randomized controlled trials (RCTs) compared with a placebo. Another two RCTs compared nitrates with alendronate. Nitrates were comparable to alendronate in increasing bone mineral density at lumbar spine (WMD = 0.00, 95% CI,-0.01-0.02; I2 = 0.0%). Besides, the most common adverse effect was headache, contributing to low adherence to therapy. CONCLUSION Our meta-analysis showed no association between nitrates use and fractures in observational studies. The results of RCTs on the usage of nitrates and their effects on BMD were inconsistent. High-quality, long-term studies are needed to clarify the efficacy of nitrates for bone health.
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Efficacy and safety of nitrate supplementation on exercise tolerance in chronic obstructive pulmonary disease: A systematic review and meta-analysis.
Yang, H, He, S, Chen, F, Liang, L, Pan, J
Medicine. 2022;(2):e28578
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BACKGROUND Exercise intolerance was prevalent in people with chronic obstructive pulmonary disease (COPD) and had a detrimental effect on the quality of life. We aimed to evaluate the efficacy and safety of nitrate supplementation in exercise tolerance of people with COPD. METHODS We searched medical databases including Cochrane Library, EMBASE, and PubMed from inception to October 2020 for randomized control trials in treating COPD with nitrate supplementation. RESULTS Nine trials were identified. Compared with placebo, nitrate supplementation has no significant effect on the following variables: exercise endurance time (standard mean difference [SMD]: 0.06; 95% confidence interval [CI]: -0.39 to 0.52; P = .79), exercise capacity (SMD: 0.30; 95% CI: -0.21 to 0.80; P = .25), oxygen consumption (SMD: -0.04; 95% CI: -0.33 to 0.25; P = .80), resting systolic blood pressure (MD: -2.84; 95% CI: -8.46 to 2.78; P = .32), systolic blood pressure after exercise (MD: -4.66; 95% CI -15.66 to 6.34; P = .41), resting diastolic blood pressure (MD: 0.89; 95% CI: -4.41 to 6.19; P = .74), diastolic blood pressure after exercise (MD: -0.21; 95% CI: -5.51 to 5.10; P = .94), heart rate (MD: -2.52; 95% CI: -7.76 to 2.73; P = .35), and arterial oxygen saturation (MD: -0.44; 95% CI: -2.38 to 1.49; P = .65). No severe adverse effects from nitrate supplementation were reported in the included trails. CONCLUSION Current evidence suggests that nitrate supplementation may be safe but ineffective for improving exercise tolerance in people with COPD.
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The Effect of Dietary Nitrate Supplementation on Isokinetic Torque in Adults: A Systematic Review and Meta-Analysis.
Lago-Rodríguez, Á, Domínguez, R, Ramos-Álvarez, JJ, Tobal, FM, Jodra, P, Tan, R, Bailey, SJ
Nutrients. 2020;(10)
Abstract
Dietary nitrate (NO3-) supplementation, which can enhance performance in exercise settings involving repeated high-intensity efforts, has been linked to improved skeletal muscle contractile function. Although muscular strength is an important component of explosive movements and sport-specific skills, few studies have quantified indices of muscular strength following NO3- supplementation, particularly isokinetic assessments at different angular velocities. We performed a systematic review and meta-analysis to determine whether dietary NO3- supplementation improves peak torque, as assessed by the gold standard method of isokinetic dynamometry, and if this effect was linked to the angular velocity imposed during the assessment. Dialnet, Directory of Open Access Journals, MEDLINE, PubMed, SciELO, Scopus, and SPORTDiscus were searched for articles using the following search strategy: (nitrate OR beet*) AND (supplement* OR nutr* OR diet*) AND (isokinetic OR strength OR "resistance exercise" OR "resistance training" OR "muscular power"). The meta-analysis of data from 5 studies with 60 participants revealed an overall effect size of -0.01 for the effect of nitrate supplementation on isokinetic peak torque, whereas trivial effect sizes ranging from -0.11 to 0.16 were observed for independent velocity-specific (90°/s, 180°/s, 270°/s, and 360°/s) isokinetic peak torque. Four of the five studies indicated that dietary NO3- supplementation is not likely to influence voluntary knee extensor isokinetic torque across a variety of angular velocities. These results suggest that NO3- supplementation does not influence isokinetic peak torque, but further work is required to elucidate the potential of NO3- supplementation to influence other indices of muscular strength, given the dearth of experimental evidence on this topic.
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Ergogenic Effect of Nitrate Supplementation: A Systematic Review and Meta-analysis.
Senefeld, JW, Wiggins, CC, Regimbal, RJ, Dominelli, PB, Baker, SE, Joyner, MJ
Medicine and science in sports and exercise. 2020;(10):2250-2261
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Although over 100 studies and reviews have examined the ergogenic effects of dietary nitrate (NO3) supplementation in young, healthy men and women, it is unclear if participant and environmental factors modulate the well-described ergogenic effects-particularly relevant factors include biological sex, aerobic fitness, and fraction of inspired oxygen (FiO2) during exercise. To address this limitation, the literature was systematically reviewed for randomized, crossover, placebo-controlled studies reporting exercise performance outcome metrics with NO3 supplementation in young, healthy adults. Of the 2033 articles identified, 80 were eligible for inclusion in the meta-analysis. Random-effects meta-analysis demonstrated that exercise performance improved with NO3 supplementation compared with placebo (d = 0.174; 95% confidence interval (CI), 0.120-0.229; P < 0.001). Subgroup analyses conducted on biological sex, aerobic fitness, and FiO2 demonstrated that the ergogenic effect of NO3 supplementation was as follows: 1) not observed in studies with only women (n = 6; d = 0.116; 95% CI, -0.126 to 0.358; P = 0.347), 2) not observed in well-trained endurance athletes (≥65 mL·kg·min; n = 26; d = 0.021; 95% CI, -0.103 to 0.144; P = 0.745), and 3) not modulated by FiO2 (hypoxia vs normoxia). Together, the meta-analyses demonstrated a clear ergogenic effect of NO3 supplementation in recreationally active, young, healthy men across different exercise paradigms and NO3 supplementation parameters; however, the effect size of NO3 supplementation was objectively small (d = 0.174). NO3 supplementation has more limited utility as an ergogenic aid in participants with excellent aerobic fitness that have optimized other training parameters. Mechanistic research and studies incorporating a wide variety of subjects (e.g., women) are needed to advance the study of NO3 supplementation; however, additional descriptive studies of young, healthy men may have limited utility.
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Effects of inorganic nitrate and nitrite consumption on cognitive function and cerebral blood flow: A systematic review and meta-analysis of randomized clinical trials.
Clifford, T, Babateen, A, Shannon, OM, Capper, T, Ashor, A, Stephan, B, Robinson, L, O'Hara, JP, Mathers, JC, Stevenson, E, et al
Critical reviews in food science and nutrition. 2019;(15):2400-2410
Abstract
We conducted a systematic review and meta-analysis of randomized clinical trials examining the effect of inorganic nitrate or nitrite supplementation on cognitive function (CF) and cerebral blood flow (CBF). Two databases (PubMed, Embase) were searched for articles from inception until May 2017. Inclusion criteria were: randomized clinical trials; participants >18 years old; trials comparing a nitrate/nitrite intervention with a control. Thirteen and nine trials were included in the meta-analysis to assess CF and CBF, respectively. Random-effects models were used and the effect size described as standardized mean differences (SMDs). A total of 297 participants (median of 23 per trial) were included for CF; 163 participants (median of 16 per trial) were included for CBF. Nitrate/nitrite supplementation did not influence CF (SMD +0.06, 95% CI: -0.06, 0.18, P = 0.32) or CBF under resting (SMD +0.14, 95% CI: -0.13, 0.41, P = 0.31), or stimulated conditions (SMD + 0.23, 95% CI: -0.11, 0.56, P = 0.19). The meta-regression showed an inverse association between duration of the intervention and CBF (P = 0.02) but no influence of age, BMI or dose (P < 0.05). Nitrate and nitrite supplementation did not modify CBF or CF. Further trials employing larger samples sizes and interventions with longer duration are warranted.
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Compound salvia pellet might be more effective and safer for chronic stable angina pectoris compared with nitrates: A systematic review and meta-analysis of randomized controlled trials.
Huiping, W, Yu, W, Pei, J, Jiao, L, Shian, Z, Hugang, J, Zheng, W, Yingdong, L
Medicine. 2019;(9):e14638
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BACKGROUND Chronic stable angina (CSA) resulted in a considerable burden for both individuals and the society. In this study we aimed to critically evaluate the effectiveness and safety of Compound salvia pellet compared with nitrates in the treatment of Chronic Stable Angina (CSA) pectoris, and to provide more credible evidence for clinical practice. METHODS A comprehensive and exhaustive search strategy was formulated to identify potential RCTs of compound salvia pellet for CSA in international and Chinese databases from their inception to July 4th, 2018. We also searched the bibliographies of relevant studies. Two reviewers independently assessed the quality of included trials by using Cochrane Risk of Bias Tool. RESULTS The literature search yielded 1849 citations and 51 RCTs (n = 4732) were included for meta-analysis after titles, abstracts and full text selection according to eligibility criteria. The pooled results suggested that compound salvia pellet was much more effective than nitrates in the improvement of angina symptoms (therapy = 4 weeks, RR = 1.23, 95%CI = [1.17, 1.30], P < .001, I = 0%; therapy = 4 weeks, RR = 1.13, 95%CI = [1.08, 1.17], P < .001, I = 45.6%), and ECG test (therapy = 4 weeks, RR = 1.24, 95%CI [1.14, 1.35], P < .001, I = 51.5%; and therapy > 4 weeks, RR = 1.30, 95%CI[1.20, 1.42], P < .001, I = 36.4%) in CSA. Compared with nitrates, the percentage of patients with adverse events significantly decreased when prescribed with compound salvia pellet (3.2% vs 17.0%). CONCLUSION Compound salvia pellet might be more effective on the improvement of angina symptoms, ECG test and with few adverse events compared with nitrates. While there are some limitations in this study, which may weaken the results, we believe the findings could provide useful information for stakeholders concerned with outcomes in patients with CSA. More rigorous RCTs with high quality are needed to confirm these findings.
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Nitrate supplementation improves physical performance specifically in non-athletes during prolonged open-ended tests: a systematic review and meta-analysis.
Campos, HO, Drummond, LR, Rodrigues, QT, Machado, FSM, Pires, W, Wanner, SP, Coimbra, CC
The British journal of nutrition. 2018;(6):636-657
Abstract
Nitrate (NO3 -) is an ergogenic nutritional supplement that is widely used to improve physical performance. However, the effectiveness of NO3 - supplementation has not been systematically investigated in individuals with different physical fitness levels. The present study analysed whether different fitness levels (non-athletes v. athletes or classification of performance levels), duration of the test used to measure performance (short v. long duration) and the test protocol (time trials v. open-ended tests v. graded-exercise tests) influence the effects of NO3 - supplementation on performance. This systematic review and meta-analysis was conducted and reported according to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. A systematic search of electronic databases, including PubMed, Web of Science, SPORTDiscus and ProQuest, was performed in August 2017. On the basis of the search and inclusion criteria, fifty-four and fifty-three placebo-controlled studies evaluating the effects of NO3 - supplementation on performance in humans were included in the systematic review and meta-analysis, respectively. NO3 - supplementation was ergogenic in non-athletes (mean effect size (ES) 0·25; 95 % CI 0·11, 0·38), particularly in evaluations of performance using long-duration open-ended tests (ES 0·47; 95 % CI 0·23, 0·71). In contrast, NO3 - supplementation did not enhance the performance of athletes (ES 0·04; 95 % CI -0·05, 0·15). After objectively classifying the participants into different performance levels, the frequency of trials showing ergogenic effects in individuals classified at lower levels was higher than that in individuals classified at higher levels. Thus, the present study indicates that dietary NO3 - supplementation improves physical performance in non-athletes, particularly during long-duration open-ended tests.
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The Nitrate-Independent Blood Pressure-Lowering Effect of Beetroot Juice: A Systematic Review and Meta-Analysis.
Bahadoran, Z, Mirmiran, P, Kabir, A, Azizi, F, Ghasemi, A
Advances in nutrition (Bethesda, Md.). 2017;(6):830-838
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Beetroot is considered a complementary treatment for hypertension because of its high content of inorganic NO3 This systematic review and meta-analysis aimed to clarify several aspects of beetroot juice supplementation on systolic blood pressure (SBP) and diastolic blood pressure (DBP). We searched PubMed, Scopus, and Embase databases, and the reference lists of previous reviews. Randomized clinical trials that investigated the effects of beetroot juice on resting blood pressure in humans were recruited for quality assessment, meta-analyses, subgroup analyses, and meta-regressions; of these, 22 were conducted between 2009 and 2017 and included a total of 47 intervention (n = 650) and 43 control (n = 598) groups. Overall, SBP (-3.55 mm Hg; 95% CI: -4.55, -2.54 mm Hg) and DBP (-1.32 mm Hg; 95% CI: -1.97, -0.68 mm Hg) were significantly lower in the beetroot juice-supplemented groups than in the control groups. The mean difference of SBP was larger between beetroot juice-supplemented and control groups in the longer than in the shorter (≥14 compared with <14 d) study durations (-5.11 compared with -2.67 mm Hg) and the highest compared with the lowest (500 compared with 70 and 140 mL/d) doses of beetroot juice (-4.78 compared with -2.37 mm Hg). A positive correlation was observed between beetroot juice doses and the mean differences of blood pressures. In contrast, a smaller effect size of blood pressures was observed after supplementation with higher NO3 (milligrams per 100 mL beetroot juice). A weak effect size was observed in a meta-analysis of trials that used NO3-depleted beetroot juice as a placebo compared with other interventions (-3.09 compared with -4.51 mm Hg for SBP and -0.81 compared with -2.01 mm Hg for DBP). Our results demonstrate the blood pressure-lowering effects of beetroot juice and highlight its potential NO3-independent effects.
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Association between dietary nitrate and nitrite intake and sitespecific cancer risk: evidence from observational studies.
Xie, L, Mo, M, Jia, HX, Liang, F, Yuan, J, Zhu, J
Oncotarget. 2016;(35):56915-56932
Abstract
Epidemiological studies have reported inconsistent findings on the association between dietary nitrate and nitrite intake and cancer risk. We performed a meta-analysis of epidemiological studies to summarize available evidence on the association between dietary nitrate and nitrite intake and cancer risk from published prospective and case-control studies. PubMed database was searched to identify eligible publications through April 30th, 2016. Study-specific relative risks (RRs) with corresponding 95% confidence interval (CI) from individual studies were pooled by using random- or fixed- model, and heterogeneity and publication bias analyses were conducted. Data from 62 observational studies, 49 studies for nitrates and 51 studies for nitrites, including a total of 60,627 cancer cases were analyzed. Comparing the highest vs. lowest levels, dietary nitrate intake was inversely associated with gastric cancer risk (RR = 0.78; 95%CI = 0.67-0.91) with moderate heterogeneity (I2 = 42.3%). In contrast, dietary nitrite intake was positively associated with adult glioma and thyroid cancer risk with pooled RR of 1.21 (95%CI = 1.03-1.42) and 1.52 (95%CI = 1.12-2.05), respectively. No significant associations were found between dietary nitrate/nitrite and cancers of the breast, bladder, colorectal, esophagus, renal cell, non-Hodgkin lymphoma, ovarian, and pancreas. The present meta-analysis provided modest evidence that positive associations of dietary nitrate and negative associations of dietary nitrite with certain cancers.
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Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis.
Lara, J, Ashor, AW, Oggioni, C, Ahluwalia, A, Mathers, JC, Siervo, M
European journal of nutrition. 2016;(2):451-459
Abstract
BACKGROUND Diets rich in inorganic nitrate are associated with lower blood pressure, an effect that may be mediated by an improvement of endothelial function (EF). Therefore, a systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted to examine the effects of inorganic nitrate and beetroot supplementation on measures of EF. METHODS MEDLINE, EMBASE and Scopus databases were searched from inception until November 2014. Specific inclusion criteria were as follows: (1) RCTs; (2) trials comparing inorganic nitrate or beetroot supplementation with placebo control groups; and (3) trials reporting effects of these interventions on outcomes of vascular function. Random-effect models were used to assess the pooled effect sizes showed as standardised mean differences (SMD). RESULTS Nine crossover trials and three parallel trials met our inclusion criteria. The trials were conducted between 2008 and 2014 and included a total of 246 participants with 10-64 participants per study. The duration of each intervention ranged from 1.5 h to 28 days. Inorganic nitrate and beetroot consumption was associated with an improvement in vascular function (SMD 0.36; 95 % CI 0.16, 0.56; P < 0.001). The effect on EF was significantly associated with the dose of inorganic nitrate (β = 0.04, SE = 0.01, P < 0.001), age (β = -0.01, SE = 0.004, P = 0.02), baseline BMI (β = -0.04, SE = 0.02, P = 0.05) and systolic BP (β = -0.01, SE = 0.005, P = 0.02). CONCLUSIONS Inorganic nitrate and beetroot supplementation was associated with beneficial effects on EF. These effects appear to be reduced in older subjects and in subjects with greater cardiometabolic risk.