Nitrate ingestion blunts the increase in blood pressure during cool air exposure: a double-blind, placebo-controlled, randomized, crossover trial.

Cold exposure increases blood pressure (BP) and salivary flow rate (SFR). Increased cold-induced SFR would be hypothesized to enhance oral nitrate delivery for reduction to nitrite by oral anaerobes and to subsequently elevate plasma [nitrite] and nitric oxide bioavailability. We tested the hypothesis that dietary nitrate supplementation would increase plasma [nitrite] and lower BP to a greater extent in cool compared with normothermic conditions. Twelve males attended the laboratory on four occasions. Baseline measurements were completed at 28°C. Subsequently, participants ingested 140 mL of concentrated nitrate-rich (BR; ∼13 mmol nitrate) or nitrate-depleted (PL) beetroot juice. Measurements were repeated over 3 h at either 28°C (Norm) or 20°C (Cool). Mean skin temperature was lowered compared with baseline in PL-Cool and BR-Cool. SFR was greater in BR-Norm, PL-Cool, and BR-Cool than PL-Norm. Plasma [nitrite] at 3 h was higher in BR-Cool (592 ± 239 nM) versus BR-Norm (410 ± 195 nM). Systolic BP (SBP) at 3 h was not different between PL-Norm (117 ± 6 mmHg) and BR-Norm (113 ± 9 mmHg). SBP increased above baseline at 1, 2, and 3 h in PL-Cool but not BR-Cool. These results suggest that BR consumption is more effective at increasing plasma [nitrite] in cool compared with normothermic conditions and blunts the rise in BP following acute cool air exposure, which might have implications for attenuating the increased cardiovascular strain in the cold.NEW & NOTEWORTHY Compared with normothermic conditions, acute nitrate ingestion increased plasma [nitrite], a substrate for oxygen-independent nitric oxide generation, to a greater extent during cool air exposure. Systolic blood pressure was increased during cool air exposure in the placebo condition with this cool-induced blood pressure increase attenuated after acute nitrate ingestion. These findings improve our understanding of environmental factors that influence nitrate metabolism and the efficacy of nitrate supplementation to lower blood pressure.

Trimethylamine N-Oxide Concentration and Blood Pressure in Young Healthy Men and Women: A Replicated Crossover Study.

Trimethylamine N-oxide (TMAO), a gut-derived metabolite and marker of gut dysbiosis, has been linked to hypertension. Blood pressure is proposed to be elevated in hormonal contraceptive users and males compared to age-matched eumenorrheic females, but the extent to which TMAO differs between these populations has yet to be investigated. Peripheral and central blood pressure were measured, with the latter determined via applanation tonometry, and plasma TMAO concentration was assessed using liquid chromatography-tandem mass spectrometry. The following variables were assessed on two occasions in each of the following conditions: the early follicular phase (EFP) and mid-luteal phase (MLP) in eumenorrheic women (n = 13), and the pill-free interval (INACTIVE) and pill consumption days (ACTIVE) in women using oral contraceptive pills (n = 12), and in men (n = 22). Briefly, 17-ß-estradiol and progesterone concentrations were quantified via ELISA in all females. There were no differences in TMAO concentration between EFP (2.9 ± 1.7 µmol/L) and MLP (3.2 ± 1.1 µmol/L), between INACTIVE (3.3 ± 2.9 µmol/L) and ACTIVE (2.3 ± 1.1 µmol/L) days, or between men (3.0 ± 1.8 µmol/L), eumenorrheic women (3.0 ± 1.3 µmol/L) and contraceptive users (2.8 ± 1.4 µmol/L). Blood pressure was consistent across the menstrual cycle and pill days, but brachial systolic blood pressure was higher in males than females. There were no differences in brachial diastolic blood pressure or central blood pressure between the sexes. Repeated measures of TMAO, blood pressure, 17-ß-estradiol and progesterone were consistent in all populations. These findings suggest that the link between TMAO and blood pressure is limited in healthy young adults.

Elderberry extract improves molecular markers of endothelial dysfunction linked to atherosclerosis.

Endothelial dysfunction (ED), secondary to diminished nitric oxide (NO) production and oxidative stress, is an early subclinical marker of atherosclerosis. Reduced NO bioavailability enhances the adhesion of monocytes to endothelial cells and promotes atherosclerosis. Elderberry extract (EB) is known to contain high levels of anthocyanins which could exert vascular protective effects. Specifically, we investigated the functional capacity of EB on various markers of ED. Human umbilical vein endothelial cells (HUVEC) were pretreated with EB 50 µg/mL and stimulated with TNF-α 10 ng/mL. Cell viability, apoptosis, oxidative stress; eNOS, Akt, Nrf2, NOX-4, and NF-κB at the protein level were measured. A co-culture model was used to determine whether EB could prevent the adhesion of monocytes (THP-1) to HUVECs. Moreover, the expression of adhesion molecules and pro-inflammatory cytokines were also measured. It was demonstrated that EB prevented TNF-α induced apoptosis and reactive oxygen species production in HUVECs. Additionally, EB upregulated Akt and eNOS activity, and Nrf2 expression in response to TNF-α, whereas it decreased NOX-4 expression and NF-κB activity. EB prevented the adhesion of monocytes to HUVECs, as well as reduced IL-6 and MCP-1 levels, which was associated with inhibition of VCAM-1 expression. Our results demonstrate that EB upregulates key cellular markers of endothelial function and ameliorates markers of ED. EB could be used as a potential nutritional aid for preventing atherosclerosis progression.

Anthocyanins and Vascular Health: A Matter of Metabolites.

Anthocyanins are a subgroup of flavonoid polyphenols previously investigated for improving cardiovascular health and preventing the development of endothelial dysfunction. However, their poor bioavailability raises the question of whether the observed biological activity is due to their metabolites. Phenolic metabolites can reach higher plasma concentrations and can persist in the circulation for periods much longer than their original anthocyanin form; therefore, the biological activity and health promoting effects of anthocyanins may differ from their metabolites. To address this, recent studies have facilitated different cell models, in vivo studies and explored physiologically relevant concentrations to better understand their mechanisms of action. The criteria were chosen based on previous reports demonstrating that anthocyanins can improve endothelial function via modulation of the Akt-endothelial nitric oxide synthase pathway and transcription factors Nrf2 and NF-κB, which made it critical to assess the phenolic metabolites' modes of action via these pathways. This review demonstrates how phenolic metabolites differ in bioactivity from their precursor anthocyanin, demonstrating improved endothelial function in response to inflammatory mediators at concentrations that are tolerated in vivo. The review highlights the crucial need for further studies to focus on improving the bioavailability of metabolites in isolation and explore the effect of metabolites in mixtures.

Elderberries as a potential supplement to improve vascular function in a SARS-CoV-2 environment.

Coronavirus disease 2019 (COVID-19) pandemic has been triggered by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Although recent studies demonstrate that SARS-CoV-2 possibly does not directly infect endothelial cells (EC), the endothelium may be affected as a secondary response due to the damage of neighboring cells, circulating pro-inflammatory cytokines, and/or other mechanisms. Long-term COVID-19 symptoms specifically nonrespiratory symptoms are due to the persistence of endothelial dysfunction (ED). Based on the literature, anthocyanins a major subgroup of flavonoid polyphenols found in berries, have been well researched for their vascular protective properties as well as the prevention of cardiovascular disease (CVD)-related deaths. Elderberries have been previously used as a natural remedy for treating influenza, cold, and consequently cardiovascular health due to a high content of cyanidin-3-glucoside (C3G) a major anthocyanin found in the human diet. The literature reported many studies demonstrating that EE has both antiviral and vascular protective properties that should be further investigated as a nutritional component used against the (in)direct effect of SARS-CoV-2 in vascular function. PRACTICAL APPLICATIONS: While previous work among the literature looks promising and builds a suggestion for investigating elderberry extract (EE) against COVID-19, further in vitro and in vivo research is required to fully evaluate EE mechanisms of action and its use as a supplement to aid current therapies.

Dietary Nitrate Supplementation Enhances Performance and Speeds Muscle Deoxyhaemoglobin Kinetics during an End-Sprint after Prolonged Moderate-Intensity Exercise.

Short-term dietary nitrate (NO3−) supplementation has the potential to enhance performance during submaximal endurance, and short-duration, maximal-intensity exercise. However, it has yet to be determined whether NO3− supplementation before and during submaximal endurance exercise can improve performance during a short-duration, maximal-intensity end-sprint. In a randomised, double-blind, crossover study, 9 recreationally active men ingested NO3−-rich (BR: 8 mmol NO3−/day) and NO3−-depleted (PL: 0.75 mmol NO3−/day) beetroot powder for 7 days. On day 7, participants completed 2 h of moderate-intensity cycling, which immediately transitioned into a 60 s maximal-intensity end-sprint, with supplements ingested 2 h before and 1 h into the moderate-intensity exercise bout. Plasma [NO3−] and [NO2−] were higher in BR compared to PL pre- and post-exercise (p < 0.05). Post-exercise plasma [NO3−] was higher than pre-exercise (562 ± 89 µM vs. 300 ± 73 µM; p < 0.05) and plasma [NO2−] was not significantly different pre- (280 ± 58 nM) and post-exercise (228 ± 63 nM) in the BR condition (p > 0.05). Mean power output during the final 30 s of the end-sprint was greater after BR (390 ± 38 W) compared to PL (365 ± 41 W; p < 0.05). There were no differences between BR and PL in any muscle oxygenation variables during moderate-intensity cycling (p > 0.05), but muscle [deoxyhaemoglobin] kinetics was faster during the end-sprint in BR (6.5 ± 1.4 s) compared to PL (7.3 ± 1.4 s; p < 0.05). These findings suggest that NO3− supplementation has the potential to improve end-sprint performance in endurance events when ingested prior to and during exercise.

Potential Benefits of Berry Anthocyanins on Vascular Function.

Cardiovascular disease (CVD), such as hypertension and atherosclerosis, is the leading cause of global death. Endothelial dysfunction (ED) is a strong predictor for most CVD making it a therapeutic target for both drug and nutrition interventions. It has been previously shown that polyphenols from wine and grape extracts possess vasodilator activities, due to the increased expression and phosphorylation of the endothelial nitric oxide synthase (eNOS), and consequent vasodilator nitric oxide (NO) production. This is vital in the prevention of ED, as NO production contributes to the maintenance of endothelial homeostasis. Moreover, polyphenols have the ability to inhibit reactive oxygen species (ROS), which can cause oxidative stress, as well as suppress the upregulation of inflammatory markers within the endothelium. However, while the majority of the research has focused on red wine, this has overshadowed the potential of other nutritional components for targeting ED, such as the use of berries. Berries are high in anthocyanin flavonoids a subtype of polyphenols with studies suggesting improved vascular function as a result of inducing NO production and reducing oxidative stress and inflammation. This review focuses on the protective effects of berries within the vasculature.

The Efficacy of Administering Fruit-Derived Polyphenols to Improve Health Biomarkers, Exercise Performance and Related Physiological Responses.

Polyphenols are secondary metabolites involved in a myriad of critical processes in plants. Over recent decades, special attention has been paid to the anti-oxidative role of fruit-derived polyphenols in the human diet, with evidence supporting the contribution of polyphenols in the prevention of numerous non-communicable disease outcomes. However, due to the low concentration in biological fluids in vivo, the antioxidant properties of polyphenols seem to be related to an enhanced endogenous antioxidant capacity induced via signaling through the nuclear respiratory factor 2 pathway. Polyphenols also seem to possess anti-inflammatory and antioxidant properties and have been shown to enhance vascular function via nitric oxide mediated mechanisms. Consequently, there is rationale to support fruit-derived polyphenol supplementation to enhance exercise performance, possibly via improved muscle perfusion. Fruit-derived polyphenol supplementation in exercise studies have included a variety of fruits, e.g., New Zealand blackcurrant, pomegranate, and cherry, in the form of extracts (multicomponent or purified), juices and infusions to varying degrees of benefit. For example, research has yet to link the health-related benefits of black elderberry (Sambucus nigra L.) ingestion to exercise performance in spite of the purported health benefits associated with black elderberry provision in vitro and in vivo models, which has been attributed to their high antioxidant capacity and polyphenol content. This review summarizes the existing evidence supporting a beneficial effect of fruit-derived polyphenols on various biological processes and outlines the potential for black elderberry ingestion to improve nitric oxide production, exercise performance, and the associated physiological responses before-, during- and post-exercise.

Markers of oxidative stress, skeletal muscle mass and function, and their responses to resistance exercise training in older adults.

BACKGROUND: Oxidative stress (OS) negatively affects skeletal muscle homeostasis in experimental models of ageing. However, little is known about the associations between circulating OS markers and parameters of muscle mass and function, and their responses to exercise training, in humans. METHODS: Maximal voluntary contraction (MVC, primary outcome) and isokinetic torque of the knee extensors at 30°â€¯s-1 (MIT), muscle cross-sectional area (MCSA) and quality (MQ, secondary outcomes), and plasma concentrations of malondialdehyde (MDA, pro-OS), homocysteine (HCY, pro-OS), taurine (TAU, anti-OS), and protein sulphydryl groups (PSH, anti-OS) were measured in 27 healthy older males and 23 females at baseline and after an 18-week resistance exercise program, with or without a nutritional intervention (fish oil vs. placebo). RESULTS: After adjusting for age, glomerular filtration rate, and nutritional intervention, there were no significant correlations between baseline OS markers and muscle parameters, barring a positive association between TAU and MIT in females (r = 0.53, P = .035) and between MDA and MCSA in males (r = 0.69, P = .001). Training did not significantly change OS markers, except for a reduction in MDA in females (-0.27 µmol/L, 95% CI -0.51 to -0.02, P = .034). In females, there were significant correlations between baseline MDA and exercise-induced changes in MVC (P = .018), baseline TAU and changes in MCSA (P = .026), and baseline HCY and changes in MCSA (P = .046) and MQ (P = .022). In males, baseline MDA was significantly associated with exercise-induced changes in MVC (P = .040). CONCLUSIONS: Plasma MDA, HCY, and TAU were significantly associated with baseline and/or exercise-induced changes in muscle mass and function in healthy older adults, primarily in females. Pending further confirmation in other populations, specific OS markers, particularly MDA, might predict muscle responses to resistance exercise programs in old age.

Fit with good fat? The role of n-3 polyunsaturated fatty acids on exercise performance.

N-3 PUFA (n-3) polyunsaturated fatty acids (PUFA) are a family of fatty acids mainly found in oily fish and fish oil supplements. The effects of n-3 PUFA on health are mainly derived from its anti-inflammatory proprieties and its influence on immune function. Lately an increased interest in n-3 PUFA supplementation has reached the world of sport nutrition, where the majority of athletes rely on nutrition strategies to improve their training and performance. A vast amount of attention is paid in increasing metabolic capacity, delaying the onset of fatigue, and improving muscle hypertrophy and neuromuscular function. Nutritional strategies are also frequently considered for enhancing recovery, improving immune function and decreasing oxidative stress. The current review of the literature shows that data regarding the effects of n-3PUFA supplementation are conflicting and we conclude that there is, therefore, not enough evidence supporting a beneficial role on the aforementioned aspects of exercise performance.

Sex differences in the effect of fish-oil supplementation on the adaptive response to resistance exercise training in older people: a randomized controlled trial.

BACKGROUND: Resistance exercise increases muscle mass and function in older adults, but responses are attenuated compared with younger people. Data suggest that long-chain n-3 polyunsaturated fatty acids (PUFAs) may enhance adaptations to resistance exercise in older women. To our knowledge, this possibility has not been investigated in men. OBJECTIVE: We sought to determine the effects of long-chain n-3 PUFA supplementation on resistance exercise training-induced increases in muscle mass and function and whether these effects differ between older men and women. DESIGN: Fifty men and women [men: n = 27, mean ± SD age: 70.6 ± 4.5 y, mean ± SD body mass index (BMI; in kg/m2): 25.6 ± 4.2; women: n = 23, mean ± SD age: 70.7 ± 3.3 y, mean ± SD BMI: 25.3 ± 4.7] were randomly assigned to either long-chain n-3 PUFA (n = 23; 3 g fish oil/d) or placebo (n = 27; 3 g safflower oil/d) and participated in lower-limb resistance exercise training twice weekly for 18 wk. Muscle size, strength, and quality (strength per unit muscle area), functional abilities, and circulating metabolic and inflammatory markers were measured before and after the intervention. RESULTS: Maximal isometric torque increased after exercise training to a greater (P < 0.05) extent in the long-chain n-3 PUFA group than in the placebo group in women, with no differences (P > 0.05) between groups in men. In both sexes, the effect of exercise training on maximal isokinetic torque at 30, 90, and 240° s-1, 4-m walk time, chair-rise time, muscle anatomic cross-sectional area, and muscle fat did not differ (P > 0.05) between groups. There was a greater (P < 0.05) increase in muscle quality in women after exercise training in the long-chain n-3 PUFA group than in the placebo group, with no such differences in men (P > 0.05). Long-chain n-3 PUFAs resulted in a greater decrease (P < 0.05) than the placebo in plasma triglyceride concentrations in both sexes, with no differences (P > 0.05) in glucose, insulin, or inflammatory markers. CONCLUSION: Long-chain n-3 PUFA supplementation augments increases in muscle function and quality in older women but not in older men after resistance exercise training. This trial was registered at clinicaltrials.gov as NCT02843009.

Sex differences in the response to resistance exercise training in older people.

Resistance exercise training is known to be effective in increasing muscle mass in older people. Acute measurement of protein metabolism data has indicated that the magnitude of response may differ between sexes. We compared adaptive responses in muscle mass and function to 18 weeks resistance exercise training in a cohort of older (>65 years) men and women. Resistance exercise training improved knee extensor maximal torque, 4 m walk time, time to complete five chair rises, muscle anatomical cross-sectional area (ACSA) and muscle quality with no effect on muscle fat/water ratio or plasma glucose, insulin, triacylglycerol, IL-6, and TNF-α Differences between sexes were observed for knee extensor maximal torque and muscle quality with greater increases observed in men versus women (P < 0.05). Maximal torque increased by 15.8 ± 10.6% in women and 41.7 ± 25.5% in men, whereas muscle quality increased by 8.8 ± 17.5% in women and by 33.7 ± 25.6% in men. In conclusion, this study has demonstrated a difference in the magnitude of adaptation, of some of the outcome measures employed, in response to 18 weeks of resistance exercise training between men and women. The mechanisms underlying this observation remain to be established.

The Effect of Krill Oil Supplementation on Exercise Performance and Markers of Immune Function.

BACKGROUND: Krill oil is a rich source of the long-chain n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which may alter immune function after exercise. The aim of the study was to determine the effects of krill oil supplementation on post exercise immune function and performance. METHODS: Nineteen males and 18 females (age: 25.8 ± 5.3 years; mean ± S.D.) were randomly assigned to 2 g/day of krill oil (n = 18) or placebo (n = 19) supplementation for 6 weeks. A maximal incremental exercise test and cycling time trial (time to complete set amount of work) were performed pre-supplementation with the time trial repeated post-supplementation. Blood samples collected pre- and post- supplementation at rest, and immediately, 1 and 3h post-exercise. Plasma IL-6 and thiobarbituric acid reactive substances (TBARS) concentrations and, erythrocyte fatty acid composition were measured. Natural killer (NK) cell cytotoxic activity and peripheral blood mononuclear cell (PBMC) IL-2, IL-4, IL-10, IL-17 and IFNγ production were also measured. RESULTS: No effects of gender were noted for any variable. PBMC IL-2 and NK cell cytotoxic activity were greater (P < 0.05) 3h post exercise in the krill oil compared to the control group. Plasma IL-6 and TBARS, PBMC IL-4, IL-10, IL-17 and IFNγ production, along with performance and physiological measures during exercise, were not different between groups. CONCLUSION: Six weeks of krill oil supplementation can increase PBMC IL-2 production and NK cell cytotoxic activity 3h post-exercise in both healthy young males and females. Krill oil does not modify exercise performance.

Effects of interval and continuous training on O2 uptake kinetics during severe-intensity exercise initiated from an elevated metabolic baseline.

The purpose of this study was to test the hypothesis that Vo2 kinetics would be speeded to a greater extent following repeated sprint training (RST), compared with continuous endurance training (ET), in the transition from moderate- to severe-intensity exercise. Twenty-three recreationally active subjects were randomly assigned to complete six sessions of ET (60-110 min of moderate-intensity cycling) or RST (four to seven 30-s all-out Wingate tests) over a 2-wk period. Subjects completed three identical work-to-work cycling exercise tests before and after the intervention period, consisting of baseline cycling at 20 W followed by sequential step increments to moderate- and severe-intensity work rates. The severe-intensity bout was continued to exhaustion on one occasion and was followed by a 60-s all-out sprint on another occasion. Phase II pulmonary Vo2 kinetics were speeded by a similar magnitude in both the lower (ET pre, 28 ± 4; ET post, 22 ± 4 s; RST pre, 25 ± 8; RST post, 20 ± 7 s) and upper (ET pre, 50 ± 10; ET post, 39 ± 11 s; RST pre, 54 ± 7; RST post, 40 ± 11 s) steps of the work-to-work test following ET and RST (P < 0.05). The tolerable duration of exercise and the total amount of sprint work completed in the exercise performance test were also similarly enhanced by ET and RST (P < 0.05). Therefore, ET and RST provoked comparable improvements in Vo2 kinetics and exercise performance in the transition from an elevated baseline work rate, with RST being a more time-efficient approach to elicit these adaptations.

Estimation of the anaerobic threshold from heart rate variability in an incremental swimming test.

This study aimed to evaluate, in swimming, the agreement between the anaerobic threshold (AT) as determined from the analysis of blood lactate concentration ([La]) and from a new method based on the heart rate (HR) variability (HRV). Fourteen high-level swimmers completed an incremental 7 × 200-m front crawl test, during which the HRV was measured continuously and [La] was collected after each step. To individuate the AT, the trends of the high-frequency HRV spectral power (HFPOW) and of the fraction of HFPOW relative to the respiratory sinus arrhythmia (HFPOW-RSA) were analyzed. In all the subjects, an abrupt increase of both HFPOW and HFPOW-RSA was observed and associated with the AT. The AT parameters determined, respectively, from [La] and HFPOW-RSA were similar (p > 0.05) and highly correlated (HR: 182.0 ± 8.1 vs. 181.1 ± 8.2 b·min, r = 0.93, 95% limits of agreement [LoA]: -6.7 to 4.9 b·min; velocity: 1.47 ± 0.11 vs. 1.47 ± 0.11 m·s, r = 0.98, 95% LoA: -0.05 to 0.05 m·s). Instead, the AT HR and velocity obtained from HFPOW (179.2 ± 8.4 b·min; 1.45 ± 0.11 m·s) were correlated to the corresponding parameters determined from [La] (HR: r = 0.84; velocity: r = 0.94) but underestimated them slightly (95% LoA: -11.9 to 6.3 b·min and -0.11 to 0.05 m·s). These results demonstrate that the AT can be assessed from the HRV in swimming, providing an important testing tool for coaches. Furthermore, using the actual respiratory spectral component, rather than the total HF spectral power, allows us to obtain a more accurate estimate of AT parameters.