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Inorganic nitrate supplementation and blood flow restricted exercise tolerance in post-menopausal women.

ABSTRACT: Exercise tolerance appears to benefit most from dietary nitrate (NO₃^-) supplementation when muscle oxygen (O₂) availability is low. Using a double-blind, randomized cross-over design, we tested the hypothesis that acute NO₃^- supplementation would improve blood flow restricted exercise duration in post-menopausal women, a population with reduced endogenous nitric oxide bioavailability. Thirteen women (57-76 yr) performed rhythmic isometric handgrip contractions (10% MVC, 30 per min) during progressive forearm blood flow restriction (upper arm cuff gradually inflated 20 mmHg each min) on three study visits, with 7-10 days between visits. Approximately one week following the first (familiarization) visit, participants consumed 140 ml of NO₃^- concentrated (9.7 mmol, 0.6 gm NO₃^-) or NO₃^-depleted beetroot juice (placebo) on separate days (≥7 days apart), with handgrip exercise beginning 100 min post-consumption. Handgrip force recordings were analyzed to determine if NO₃^- supplementation enhanced force development as blood flow restriction progressed. Nitrate supplementation increased plasma NO₃^- (16.2-fold) and NO₂^- (4.2-fold) and time to volitional fatigue (61.8 ± 56.5 s longer duration vs. placebo visit; p = 0.03). Nitrate supplementation increased the rate of force development as forearm muscle ischemia progressed (p = 0.023 between 50 and 75% of time to fatigue) with non-significant effects thereafter (p = 0.052). No effects of nitrate supplementation were observed for mean duration of contraction or relaxation rates (all p > 0.150). These results suggest that acute NO₃^- supplementation prolongs time-to-fatigue and speeds grip force development during progressive forearm muscle ischemia in postmenopausal women.

SUBMITTER: Proctor DN

PROVIDER: S-EPMC9062890 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Inorganic nitrate supplementation and blood flow restricted exercise tolerance in post-menopausal women.

Proctor David N DN Neely Kristina A KA Mookerjee Swapan S Tucker Jacqueline J Somani Yasina B YB Flanagan Michael M Kim-Shapiro Daniel B DB Basu Swati S Muller Matthew D MD Jin-Kwang Kim Danielle D

Nitric oxide : biology and chemistry 20220228

Exercise tolerance appears to benefit most from dietary nitrate (NO3-) supplementation when muscle oxygen (O2) availability is low. Using a double-blind, randomized cross-over design, we tested the hypothesis that acute NO3- supplementation would improve blood flow restricted exercise duration in post-menopausal women, a population with reduced endogenous nitric oxide bioavailability. Thirteen women (57-76 yr) performed rhythmic isometric ha ...[more]

PMID: 35240317

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Project description:PurposeConsumption of nitrate-rich beetroot juice can lower blood pressure in peripheral as well as central arteries and may exert additional hemodynamic benefits (e.g. reduced aortic wave reflections). The specific influence of nitrate supplementation on arterial pressures and aortic wave properties in postmenopausal women, a group that experiences accelerated increases in these variables with age, is unknown. Accordingly, the primary aim of this study was to determine the effect of consuming nitrate-rich beetroot juice on resting brachial and aortic blood pressures (BP) and pulse wave characteristics in a group of healthy postmenopausal women, in comparison to a true (nitrate-free beetroot juice) placebo.MethodsBrachial (oscillometric cuff) and radial (SphygmoCor) pressures and derived-aortic waveforms were measured during supine rest in thirteen healthy postmenopausal women (63 ± 1 yr) before and 100 min after consumption of 140 ml of either nitrate-rich (9.7 mmol, 0.6 gm NO3-) or nitrate-depleted beetroot juice on randomized visits approximately 10 days apart (cross-over design). Ten young premenopausal women (22 ± 1 yr) served as a reference (non-supplemented) cohort.ResultsBrachial and derived-aortic variables showed the expected age-associated differences in these women (all p < 0.05). In post-menopausal women, nitrate supplementation reduced (p < 0.05 vs. placebo visit) brachial systolic BP (BRnitrate -4.9 ± 2.1 mmHg vs BRplacebo +1.1 ± 1.8 mmHg), brachial mean BP (BRnitrate -4.1 ± 1.7 mmHg vs BRplacebo +0.9 ± 1.3 mmHg), aortic systolic BP (BRnitrate -6.3 ± 2.0 mmHg vs BRplacebo +0.5 ± 1.7 mmHg) and aortic mean BP (BRnitrate -4.1 ± 1.7 mmHg vs BRplacebo +0.9 ± 1.3 mmHg), and increased pulse pressure amplification (BRnitrate +4.6 ± 2.0% vs BRplacebo +0.7 ± 2.5%, p = 0.04), but did not alter aortic pulse wave velocity or any other derived-aortic variables (e.g., augmentation pressure or index).ConclusionsDietary nitrate supplementation favorably modifies aortic systolic and mean blood pressure under resting conditions in healthy postmenopausal women. Acute supplementation of nitrate does not, however, appear to restore indices of aortic stiffness in this group. Future work should evaluate chronic, long-term effects of this non-pharmacological supplement.

Project description:BackgroundInorganic nitrate (NO3-) supplementation is purported to benefit short-term exercise performance, but it is unclear whether NO3- improves longer-term exercise training responses (such as improvements in VO2peak or time to exhaustion (TTE)) versus exercise training alone. The purpose of this systematic review and meta-analysis was to determine the effects of NO3- supplementation combined with exercise training on VO2peak and TTE, and to identify potential factors that may impact outcomes.MethodsElectronic databases (PubMed, Medscape, and Web of Science) were searched for articles published through June 2022 with article inclusion determined a priori as: (1) randomized placebo-controlled trials, (2) exercise training lasted at least three weeks, (3) treatment groups received identical exercise training, (4) treatment groups had matched VO2peak at baseline. Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Standardized mean difference (SMD) with 95% confidence intervals (CI) were calculated using restricted maximum likelihood estimation between pre- and post-training differences in outcomes. Moderator subgroup and meta-regression analyses were completed to determine whether the overall effect was influenced by age, sex, NO3- dosage, baseline VO2peak, health status, NO3- administration route, and training conditions.ResultsNine studies consisting of eleven trials were included: n = 228 (72 females); age = 37.7 ± 21 years; VO2peak: 40 ± 18 ml/kg/min. NO3- supplementation did not enhance exercise training with respect to VO2peak (SMD: 0.18; 95% CI: -0.09, 0.44; p = 0.19) or TTE (SMD: 0.08; 95% CI: - 0.21, 0.37; p = 0.58). No significant moderators were revealed on either outcome. Subset analysis on healthy participants who consumed beetroot juice (BRJ) revealed stronger trends for NO3- improving VO2peak (p = 0.08) compared with TTE (p = 0.19), with no significant moderators. Sunset funnel plot revealed low statistical power in all trials.ConclusionsNO3- supplementation combined with exercise training may not enhance exercise outcomes such as VO2peak or TTE. A trend for greater improvement in VO2peak in healthy participants supplemented with BRJ may exist (p = 0.08). Overall, future studies in this area need increased sample sizes, more unified methodologies, longer training interventions, and examination of sex as a biological variable to strengthen conclusions.

Project description:Vitamin D and calcium supplementation have been posited to improve body composition and different formulations of calcium may impact bioavailability. However, data are lacking regarding the combinatorial effects of exercise, diet, and calcium and/or vitamin D supplementation on body composition changes in post-menopausal women. Herein, 128 post-menopausal women (51.3 ± 4.5 years, 36.4 ± 5.7 kg/m2, 46.2 ± 4.5% fat) were assigned to diet and supplement groups while participating in a supervised circuit-style resistance-training program (3 d/week) over a 14-week period. Diet groups included: (1) normal diet (CTL), (2) a low-calorie, higher protein diet (LCHP; 1600 kcal/day, 15% carbohydrates, 55% protein, 30% fat), and (3) a low-calorie, higher carbohydrate diet (LCHC; 1600 kcal/day, 55% carbohydrates, 15% protein, 30% fat). Supplement groups consisted of: (1) maltodextrin (PLA), (2) 800 mg/day of calcium carbonate (Ca), and (3) 800 mg/day of calcium citrate and malate and 400 IU/day of vitamin D (Ca+D). Fasting blood samples, body composition, resting energy expenditure, aerobic capacity, muscular strength and endurance measures were assessed. Data were analyzed by mixed factorial ANOVA with repeated measures and presented as mean change from baseline [95% CI]. Exercise training promoted significant improvements in strength, peak aerobic capacity, and blood lipids. Dieting resulted in greater losses of body mass (CTL -0.4 ± 2.4; LCHC -5.1 ± 4.2; LCHP -3.8 ± 4.2 kg) and fat mass (CTL -1.4 ± 1.8; LCHC -3.7 ± 3.7; LCHP -3.4 ± 3.4 kg). When compared to LCHC-PLA, the LCHC + Ca combination led to greater losses in body mass (PLA -4.1 [-6.1, -2.1], Ca -6.4 [-8.1, -4.7], Ca+D -4.4 [-6.4, -2.5] kg). In comparison to LCHC-Ca, the LCHC-Ca+D led to an improved maintenance of fat-free mass (PLA -0.3 [-1.4, 0.7], Ca -1.4 [-2.3, -0.5], Ca+D 0.4 [-0.6, 1.5] kg) and a greater loss of body fat (PLA -2.3 [-3.4, -1.1], Ca -1.3 [-2.3, -0.3], Ca+D -3.6 [-4.8, -2.5]%). Alternatively, no significant differences in weight loss or body composition resulted when adding Ca or Ca+D to the LCHP regimen in comparison to when PLA was added to the LCHP diet. When combined with an energy-restricted, higher carbohydrate diet, adding 800 mg of Ca carbonate stimulated greater body mass loss compared to when a PLA was added. Alternatively, adding Ca+D to the LCHC diet promoted greater% fat changes and attenuation of fat-free mass loss. Our results expand upon current literature regarding the impact of calcium supplementation with dieting and regular exercise. This data highlights that different forms of calcium in combination with an energy restricted, higher carbohydrate diet may trigger changes in body mass or body composition while no impact of calcium supplementation was observed when participants followed an energy restricted, higher protein diet.

Project description:Background Muscle ageing contributes to both loss of functional autonomy and increased morbidity. Muscle atrophy accelerates after 50 years of age, but the mechanisms involved are complex and likely result from the alteration of a variety of interrelated functions. In order to better understand the molecular mechanisms underlying muscle chronological ageing in human, we have undertaken a top-down differential proteomic approach to identify novel biomarkers after the fifth decade of age. Results Muscle samples were compared between adult (56 years) and old (78 years) post-menopausal women. In addition to total muscle extracts, low-ionic strength extracts were investigated to remove high abundance myofibrillar proteins and improve the detection of low abundance proteins. Two-dimensional gel electrophoreses with overlapping IPGs were used to improve the separation of muscle proteins. Overall, 1919 protein spots were matched between all individuals, 95 were differentially expressed and identified by mass spectrometry, and they corresponded to 67 different proteins. Our results suggested important modifications in cytosolic, mitochondrial and lipid energy metabolism, which may relate to dysfunctions in old muscle force generation. A fraction of the differentially expressed proteins were linked to the sarcomere and cytoskeleton (myosin light-chains, troponin T, ankyrin repeat domain-containing protein-2, vinculin, four and a half LIM domain protein-3), which may account for alterations in contractile properties. In line with muscle contraction, we also identified proteins related to calcium signal transduction (calsequestrin-1, sarcalumenin, myozenin-1, annexins). Muscle ageing was further characterized by the differential regulation of several proteins implicated in cytoprotection (catalase, peroxiredoxins), ion homeostasis (carbonic anhydrases, selenium-binding protein 1) and detoxification (aldo-keto reductases, aldehyde dehydrogenases). Notably, many of the differentially expressed proteins were central for proteostasis, including heat shock proteins and proteins involved in proteolysis (valosin-containing protein, proteasome subunit beta type-4, mitochondrial elongation factor-Tu). Conclusions This study describes the most extensive proteomic analysis of muscle ageing in humans, and identified 34 new potential biomarkers. None of them were previously recognized as differentially expressed in old muscles, and each may represent a novel starting point to elucidate the mechanisms of muscle chronological ageing in humans.

Project description:Patients with type 2 diabetes mellitus (T2DM) have reduced exercise capacity, indexed by lower maximal oxygen consumption (V̇o2max) and achievement of the gas exchange threshold (GET) at a lower % V̇o2max. The ubiquitous signaling molecule nitric oxide (NO) plays a multifaceted role during exercise and, as patients with T2DM have poor endogenous NO production, we investigated if inorganic nitrate/nitrite supplementation (an exogenous source of NO) improves exercise capacity in patients with T2DM. Thirty-six patients with T2DM (10F, 59 ± 9 yr, 32.0 ± 5.1 kg/m2, HbA1c = 7.4 ± 1.4%) consumed beetroot juice containing either inorganic nitrate/nitrite (4.03 mmol/0.29 mmol) or a placebo (0.8 mmol/0.00 mmol) for 8 wk. A maximal exercise test was completed before and after both interventions. V̇o2max was determined by averaging 15-s data, whereas the GET was identified using the V-slope method and breath-by-breath data. Inorganic nitrate/nitrite increased both absolute (1.96 ± 0.67 to 2.07 ± 0.75 L/min) and relative (20.7 ± 7.0 to 21.9 ± 7.4 mL/kg/min, P < 0.05 for both) V̇o2max, whereas no changes were observed following placebo (1.94 ± 0.40 to 1.90 ± 0.39 L/min, P = 0.33; 20.0 ± 4.2 to 19.7 ± 4.6 mL/kg/min, P = 0.39). Maximal workload was also increased following inorganic nitrate/nitrite supplementation (134 ± 47 to 140 ± 51 W, P < 0.05) but not placebo (138 ± 32 to 138 ± 32 W, P = 0.98). V̇o2 at the GET (1.11 ± 0.27 to 1.27 ± 0.38L/min) and the %V̇o2max in which GET occurred (56 ± 8 to 61 ± 7%, P < 0.05 for both) increased following inorganic nitrate/nitrite supplementation but not placebo (1.10 ± 0.23 to 1.08 ± 0.21 L/min, P = 0.60; 57 ± 9 to 57 ± 8%, P = 0.90) although the workload at GET did not achieve statistical significance (group-by-time P = 0.06). Combined inorganic nitrate/nitrite consumption improves exercise capacity, maximal workload, and promotes a rightward shift in the GET in patients with T2DM. This manuscript reports data from a registered Clinical Trial at ClinicalTrials.gov ID: NCT02804932.NEW & NOTEWORTHY We report that increasing nitric oxide bioavailability via 8 wk of inorganic nitrate/nitrite supplementation improves maximal aerobic exercise capacity in patients with type 2 diabetes mellitus. Similarly, we observed a rightward shift in the gas exchange threshold. Taken together, these data indicate inorganic nitrate/nitrite may serve as a means to improve fitness in patients with type 2 diabetes mellitus.

Project description:The effect of nitrate (NO3-) supplementation on blood pressure (BP) responses during large muscle mass isometric and ischaemic exercise in healthy young adults is unclear. The aim of the present study was to assess the effect of 5-day supplementation of NO3- on BP responses during a short isometric contraction and a sustained ischaemic contraction. In a randomised, double-blinded, crossover design, 14 healthy active young adults underwent BP measurements after 5 days of either NO3- (NIT) or placebo (PLA) supplementation. Beat-by-beat BP was measured at pre- and post-exercise rest, and during a short (20 s) isometric contraction at 25% maximal strength and throughout a sustained ischaemic contraction. Plasma nitrite (NO2-) concentration increased significantly after NO3- supplementation compared to placebo (475 ± 93 nmol·L-1 vs. 198 ± 46 nmol·L-1, p < 0.001, d = 3.37). Systolic BP was significantly lower at pre- (p = 0.051) and post-exercise rest (p = 0.006), during a short isometric contraction (p = 0.030), and throughout a sustained ischaemic contraction (p = 0.040) after NO3- supplementation. Mean arterial pressure was significantly lower at pre- (p = 0.004) and post-exercise rest (p = 0.043), during a short isometric contraction (p = 0.041), and throughout a sustained ischaemic contraction (p = 0.021) after NO3- supplementation. Diastolic BP was lower at pre-exercise rest (p = 0.032), but not at post-exercise rest, during a short isometric contraction, and during a sustained ischaemic contraction (all p > 0.05). Five days of NO3- supplementation elevated plasma NO2- concentration and reduced BP during a short isometric contraction and a sustained ischaemic contraction in healthy adults. These observations indicate that multiple-day nitrate supplementation can decrease BP at rest and attenuate the increased BP response during isometric exercise. These findings support that NO3- supplementation is an effective nutritional intervention in reducing SBP and MAP in healthy young males during submaximal exercise.

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Inorganic nitrate supplementation and blood flow restricted exercise tolerance in post-menopausal women.

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Inorganic nitrate supplementation and blood flow restricted exercise tolerance in post-menopausal women.

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