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Beetroot juice supplementation and exercise performance: is there more to the story than just nitrate?
Zoughaib, WS, Fry, MJ, Singhal, A, Coggan, AR
Frontiers in nutrition. 2024;:1347242
Abstract
This mini-review summarizes the comparative effects of different sources of dietary nitrate (NO3-), beetroot juice (BRJ) and nitrate salts (NIT), on physiological function and exercise capacity. Our objectives were to determine whether BRJ is superior to NIT in enhancing exercise-related outcomes, and to explore the potential contribution of other putatively beneficial compounds in BRJ beyond NO3-. We conducted a comparative analysis of recent studies focused on the impact of BRJ versus NIT on submaximal oxygen consumption (VO2), endurance performance, adaptations to training, and recovery from muscle-damaging exercise. While both NO3- sources provide benefits, there is some evidence that BRJ may offer additional advantages, specifically in reducing VO2 during high-intensity exercise, magnifying performance improvements with training, and improving recovery post-exercise. These reported differences could be due to the hypothesized antioxidant and/or anti-inflammatory properties of BRJ resulting from the rich spectrum of phytonutrients it contains. However, significant limitations to published studies directly comparing BRJ and NIT make it quite challenging to draw any firm conclusions. We provide recommendations to help guide further research into the important question of whether there is more to the story of BRJ than just NO3-.
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The influence of acute dietary nitrate supplementation on skeletal muscle fatigue and recovery in older women.
Zoughaib, WS, Hoffman, RL, Yates, BA, Moorthi, RN, Lim, K, Coggan, AR
medRxiv : the preprint server for health sciences. 2023
Abstract
Older individuals fatigue more rapidly during, and recover more slowly from, dynamic exercise. Women are particularly vulnerable to these deleterious effects of aging, which increases their risk of falling. We have shown that dietary nitrate (NO 3 - ), a source of nitric oxide (NO) via the NO 3 - → nitrite (NO 2 - ) → NO pathway, enhances muscle speed and power in older individuals in the non-fatigued state; however, it is unclear if it reduces fatigability and/or improves recoverability in this population. Using a double-blind, placebo-controlled, crossover design, we studied 18 older (age 70 ± 4 y) women who were administered an acute dose of beetroot juice (BRJ) containing either 15.6±3.6 or <0.05 mmol of NO 3 - . Blood samples were drawn throughout each ∼3 h visit for plasma NO 3 - and NO 2 - analysis. Peak torque was measured during, and periodically for 10 min after, 50 maximal knee extensions performed at 3.14 rad/s on an isokinetic dynamometer. Ingestion of NO 3 - -containing BRJ increased plasma NO 3 - and NO 2 - concentrations by 21±8 and 4±4 fold, respectively. However, there were no differences in muscle fatigue or recovery. Dietary NO 3 - increases plasma NO 3 - and NO 2 - concentrations but does not reduce fatigability during or enhance recoverability after high intensity exercise in older women.
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The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design.
Coggan, AR, Park, LK, Racette, SB, Davila-Roman, VG, Lenzen, P, Vehe, K, Dore, PM, Schechtman, KB, Peterson, LR
Contemporary clinical trials communications. 2023;:101208
Abstract
BACKGROUND Heart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF). METHODS This clinical trial is a double-blind, placebo-controlled, randomized, parallel-arm design study in which patients with HFrEF (n = 75) are randomized to receive 10 mmol potassium nitrate (KNO3) or a placebo capsule daily for 6 wk. Primary outcome measures are muscle power determined by isokinetic dynamometry and peak aerobic capacity (VO2peak) determined during an incremental treadmill exercise test. Endpoints include the acute effects of a single dose of KNO3 and longer-term effects of 6 wk of KNO3. The study is adequately powered to detect expected increases in these outcomes at P < 0.05 with 1-β>0.80. DISCUSSION The iNIX-HF phase II clinical trial will evaluate the effectiveness of inorganic nitrate supplements as a new treatment to ameliorate poor exercise capacity in HFrEF. This study also will provide critical preliminary data for a future 'pivotal', phase III, multi-center trial of the effectiveness of nitrate supplements not only for improving exercise performance, but also for improving symptoms and decreasing other major cardiovascular endpoints. The potential public health impact of identifying a new, relatively inexpensive, safe, and effective treatment that improves overall exercise performance in patients with HFrEF is significant.
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Short-term beetroot juice supplementation improves muscle speed and power but does not reduce blood pressure or oxidative stress in 65-79 y old men and women.
Zoughaib, WS, Hoffman, RL, Yates, BA, Moorthi, RN, Lim, K, Coggan, AR
Nitric oxide : biology and chemistry. 2023;:34-41
Abstract
We have previously demonstrated that acute ingestion of inorganic nitrate (NO3-)-rich beetroot juice (BRJ), a source of nitric oxide (NO) via the NO3- → nitrite (NO2-) → NO pathway, can improve muscle speed and power in older individuals. It is not known, however, whether this effect is maintained or perhaps even enhanced with repeated ingestion, or if tolerance develops as with organic nitrates, e.g., nitroglycerin. Using a double-blind, placebo-controlled, crossover design, we therefore studied 16 community-dwelling older (age 71 ± 5 y) individuals after both acute and short-term (i.e., daily for 2 wk) BRJ supplementation. Blood samples were drawn and blood pressure was measured periodically during each ∼3 h experiment, with muscle function determined using isokinetic dynamometry. Acute ingestion of BRJ containing 18.2 ± 6.2 mmol of NO3- increased plasma NO3- and NO2- concentrations 23 ± 11 and 2.7 ± 2.1-fold over placebo, respectively. This was accompanied by 5 ± 11% and 7 ± 13% increases in maximal knee extensor speed (Vmax) and power (Pmax), respectively. After daily supplementation for 2 wk, BRJ ingestion elevated NO3- and NO2- levels 24 ± 12 and 3.3 ± 4.0-fold, respectively, whereas Vmax and Pmax were 7 ± 9% and 9 ± 11% higher than baseline. No changes were observed in blood pressure or in plasma markers of oxidative stress with either acute or short-term NO3- supplementation. We conclude that both acute and short-term dietary NO3- supplementation result in similar improvements in muscle function in older individuals. The magnitudes of these improvements are sufficient to offset the decline resulting from a decade or more of aging and are therefore likely to be clinically significant.
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5.
The influence of acute dietary nitrate supplementation on skeletal muscle fatigue and recovery in older women.
Zoughaib, WS, Hoffman, RL, Yates, BA, Moorthi, RN, Lim, K, Coggan, AR
Physiological reports. 2023;(10):e15694
Abstract
Older individuals fatigue more rapidly during, and recover more slowly from, dynamic exercise. Women are particularly vulnerable to these deleterious effects of aging, which increases their risk of falling. We have shown that dietary nitrate (NO3 - ), a source of nitric oxide (NO) via the NO3 - → nitrite (NO2 - ) → NO pathway, enhances muscle speed and power in older individuals in the non-fatigued state; however, it is unclear if it reduces fatigability and/or improves recoverability in this population. Using a double-blind, placebo-controlled, crossover design, we studied 18 older (age 70 ± 4 years) women who were administered an acute dose of beetroot juice (BRJ) containing either 15.6 ± 3.6 or <0.05 mmol of NO3 - . Blood samples were drawn throughout each ~3 h visit for plasma NO3 - and NO2 - analysis. Peak torque was measured during, and periodically for 10 min after, 50 maximal knee extensions performed at 3.14 rad/s on an isokinetic dynamometer. Ingestion of NO3 - -containing BRJ increased plasma NO3 - and NO2 - concentrations by 21 ± 8 and 4 ± 4 fold, respectively. However, there were no differences in muscle fatigue or recovery. Dietary NO3 - increases plasma NO3 - and NO2 - concentrations but does not reduce fatigability during or enhance recoverability after high intensity exercise in older women.
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Effect of dietary nitrate on human muscle power: a systematic review and individual participant data meta-analysis.
Coggan, AR, Baranauskas, MN, Hinrichs, RJ, Liu, Z, Carter, SJ
Journal of the International Society of Sports Nutrition. 2021;18(1):66
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Plain language summary
Previous reviews have concluded that dietary nitrate (NO3−) improves maximal neuromuscular power in humans, but these were based on a limited number of studies. This is the first systematic review and meta-analysis evaluating the effects of dietary NO3− supplementation on muscular power in humans. The study also aims to quantify the size of this beneficial effect. 19 studies with a total of 268 participants were included. Most of these used concentrated beetroot juice as the source of NO3− given as an acute dose (short term high level). A positive effect of dietary NO3− on muscle power was observed in all 19 studies. Analyses were done on sub groups - age, sex and the amount of muscle mass engaged in the activity. Dietary NO3− intake significantly increases maximal muscle power in humans. The magnitude of this effect has practical and clinical importance; not just for athletes but also for patient groups. This effect is independent of subject age, sex, or the amount of muscle mass engaged in the activity but may be greater with acute vs. repeated dosing. Further research is needed to determine factors such as the optimal supplementation regimen and target population.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This meta-analysis lends quantitative support to previous narrative reviews that nitrate supplementation can enhance maximal power output.
- These findings are highly relevant to team and strength sport athletes, who may not otherwise be supplementing with nitrates.
- These findings are also highly relevant for older populations, where risk of falls and fractures are high and can lead to significant adverse effects on health and quality of life.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- In 2007, researchers uncovered the ingestion of dietary nitrates reduced the oxygen cost of submaximal exercise, and since, over 100 studies have examined the effects of nitrates on endurance performance.
- With regards to the impact of nitrates on maximal force output, only trivial results had been previously found.
- This review study found that while nitrates do not impact force development, they do demonstrate primary effect on the speed of muscle contraction (i.e. muscular power is the product of force x speed).
- The reviews primary finding was that nitrate intake can significantly enhance muscular power, regardless of subject age or sex.
Clinical practice applications:
- These new findings highlight the ability of dietary nitrates to improve neuromuscular power production is highly relevant for team sport athletes, due to the explosive nature of these sports with constant accelerations and decelerations during training and competition.
- In the general population, falls and fractures amongst older adults significantly reduces quality of life and costs the healthcare system hundreds of millions of pounds to treat.
- Improved contractile properties of muscle, most notably speed of contraction, may offer protection to older adults as well as the benefit of additional nitric oxide (NO) to support vascular health as well.
- The typical intake of dietary nitrates in the general population is about 31-185mg/day in Europe and 40-100mg/day in North America. Most studies use doses between 300-600mg of dietary nitrates. Increasing dietary or supplemental intake is key to achieving the neuromuscular effect.
Considerations for future research:
- The results of the present meta-analysis clearly demonstrate that dietary nitrates increases muscle power in humans, but the mechanism responsible for this effect is still unclear.
- There are notable differences between rodent and human metabolism of dietary nitrates, therefore the biochemical mechanism by which nitrate intake improves human muscle power requires additional study.
Abstract
BACKGROUND Previous narrative reviews have concluded that dietary nitrate (NO3-) improves maximal neuromuscular power in humans. This conclusion, however, was based on a limited number of studies, and no attempt has been made to quantify the exact magnitude of this beneficial effect. Such information would help ensure adequate statistical power in future studies and could help place the effects of dietary NO3- on various aspects of exercise performance (i.e., endurance vs. strength vs. power) in better context. We therefore undertook a systematic review and individual participant data meta-analysis to quantify the effects of NO3- supplementation on human muscle power. METHODS The literature was searched using a strategy developed by a health sciences librarian. Data sources included Medline Ovid, Embase, SPORTDiscus, Scopus, Clinicaltrials.gov , and Google Scholar. Studies were included if they used a randomized, double-blind, placebo-controlled, crossover experimental design to measure the effects of dietary NO3- on maximal power during exercise in the non-fatigued state and the within-subject correlation could be determined from data in the published manuscript or obtained from the authors. RESULTS Nineteen studies of a total of 268 participants (218 men, 50 women) met the criteria for inclusion. The overall effect size (ES; Hedge's g) calculated using a fixed effects model was 0.42 (95% confidence interval (CI) 0.29, 0.56; p = 6.310 × 10- 11). There was limited heterogeneity between studies (i.e., I2 = 22.79%, H2 = 1.30, p = 0.3460). The ES estimated using a random effects model was therefore similar (i.e., 0.45, 95% CI 0.30, 0.61; p = 1.064 × 10- 9). Sub-group analyses revealed no significant differences due to subject age, sex, or test modality (i.e., small vs. large muscle mass exercise). However, the ES in studies using an acute dose (i.e., 0.54, 95% CI 0.37, 0.71; p = 6.774 × 10- 12) was greater (p = 0.0211) than in studies using a multiple dose regimen (i.e., 0.22, 95% CI 0.01, 0.43; p = 0.003630). CONCLUSIONS Acute or chronic dietary NO3- intake significantly increases maximal muscle power in humans. The magnitude of this effect-on average, ~ 5%-is likely to be of considerable practical and clinical importance.
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Klotho: An Emerging Factor With Ergogenic Potential.
Arroyo, E, Troutman, AD, Moorthi, RN, Avin, KG, Coggan, AR, Lim, K
Frontiers in rehabilitation sciences. 2021;:807123
Abstract
Sarcopenia and impaired cardiorespiratory fitness are commonly observed in older individuals and patients with chronic kidney disease (CKD). Declines in skeletal muscle function and aerobic capacity can progress into impaired physical function and inability to perform activities of daily living. Physical function is highly associated with important clinical outcomes such as hospitalization, functional independence, quality of life, and mortality. While lifestyle modifications such as exercise and dietary interventions have been shown to prevent and reverse declines in physical function, the utility of these treatment strategies is limited by poor widespread adoption and adherence due to a wide variety of both perceived and actual barriers to exercise. Therefore, identifying novel treatment targets to manage physical function decline is critically important. Klotho, a remarkable protein with powerful anti-aging properties has recently been investigated for its role in musculoskeletal health and physical function. Klotho is involved in several key processes that regulate skeletal muscle function, such as muscle regeneration, mitochondrial biogenesis, endothelial function, oxidative stress, and inflammation. This is particularly important for older adults and patients with CKD, which are known states of Klotho deficiency. Emerging data support the existence of Klotho-related benefits to exercise and for potential Klotho-based therapeutic interventions for the treatment of sarcopenia and its progression to physical disability. However, significant gaps in our understanding of Klotho must first be overcome before we can consider its potential ergogenic benefits. These advances will be critical to establish the optimal approach to future Klotho-based interventional trials and to determine if Klotho can regulate physical dysfunction.
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Beetroot supplementation in women enjoying exercise together (BEE SWEET): Rationale, design and methods.
Baranauskas, MN, Altherr, CA, Gruber, AH, Coggan, AR, Raglin, JS, Gupta, SK, Carter, SJ
Contemporary clinical trials communications. 2021;:100693
Abstract
BACKGROUND Postmenopausal women exhibit higher rates of disability and cardiovascular disease (CVD) with aging compared to men. Whereas habitual exercise training is a known strategy to enhance physiologic function in men and premenopausal women, exercise-related adaptations are often modest in postmenopausal women. We propose dietary nitrate (beetroot juice) administered prior to exercise training may be a feasible approach to improve mobility and cardio-metabolic health outcomes in postmenopausal women. METHODS Our randomized, placebo-controlled study aims to determine preliminary effects sizes for changes in functional mobility and endothelium-dependent vasodilation across three study arms: exercise only (EX), exercise + placebo (EX + PL), and exercise + beetroot (EX + BR). Thirty-six postmenopausal women are recruited in small cohorts wherein group exercise is implemented to facilitate social support and adherence to an 8-week training progression. Participants are randomized to one of three study arms (n = 12 per group) following baseline assessments. Post-intervention assessments are used to determine pre-post changes in outcome measures including distance covered during a 6 min walk test, walking economy, muscle speed and power, and endothelial-dependent vasodilation as determined by flow-mediated dilation. Measures of feasibility include recruitment, retention, adherence to exercise prescription, perceived exercise session difficulty, and adverse event rates. DISCUSSION Evidence-based, translational strategies are needed to optimize exercise training-related adaptations in postmenopausal women. Findings will inform larger randomized clinical trials to determine if pre-exercise consumption of beetroot juice is an efficacious strategy to promote mobility and attenuate CVD disease risk.
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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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A Single Dose of Dietary Nitrate Increases Maximal Knee Extensor Angular Velocity and Power in Healthy Older Men and Women.
Coggan, AR, Hoffman, RL, Gray, DA, Moorthi, RN, Thomas, DP, Leibowitz, JL, Thies, D, Peterson, LR
The journals of gerontology. Series A, Biological sciences and medical sciences. 2020;(6):1154-1160
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BACKGROUND Aging results in reductions in maximal muscular strength, speed, and power, which often lead to functional limitations highly predictive of disability, institutionalization, and mortality in elderly adults. This may be partially due to reduced nitric oxide (NO) bioavailability. We, therefore, hypothesized that dietary nitrate (NO3-), a source of NO via the NO3- → nitrite (NO2-) → NO enterosalivary pathway, could increase muscle contractile function in older subjects. METHODS Twelve healthy older (age 71 ± 5 years) men and women were studied using a randomized, double-blind, placebo-controlled, crossover design. After fasting overnight, subjects were tested 2 hours after ingesting beetroot juice containing or devoid of 13.4 ± 1.6 mmol NO3-. Plasma NO3- and NO2- and breath NO were measured periodically, and muscle function was determined using isokinetic dynamometry. RESULTS N O 3 - ingestion increased (p < .001) plasma NO3-, plasma NO2-, and breath NO by 1,051% ± 433%, 138% ± 149%, and 111% ± 115%, respectively. Maximal velocity of knee extension increased (p < .01) by 10.9% ± 12.1%. Maximal knee extensor power increased (p < .05) by 4.4% ± 7.8%. CONCLUSIONS Acute dietary NO3- intake improves maximal knee extensor angular velocity and power in older individuals. These findings may have important implications for this population, in whom diminished muscle function can lead to functional limitations, dependence, and even premature death.