The impact of dietary supplements on blood pressure in older adults: A network meta-analysis of randomized controlled trials.

Purpose: The prevalence of hypertension (HTN) increases with age and there is a need for effective, evidence-based treatments for HTN among older adults. The objective of this study was to perform a network meta-analysis to evaluate the effectiveness of different forms of nutritional supplementation on reducing blood pressure in older adults. Methods: A systematic review using PubMed and Clinical Key was performed to identify randomized controlled trials (RCTs) evaluating the effects of dietary supplements on blood pressure in adults older than 65 years of age. Network meta-analysis (NMA) was used to compare and rank the effects of different supplements on systolic (sBP), diastolic (dBP), and mean (mBP) blood pressure. Supplements were ranked according to P score. Meta-regressions were conducted to examine whether treatment effects were moderated by baseline BP and supplementation duration. Findings: We identified 144 relevant studies in the literature, twelve of which met criteria for inclusion in NMA. The included studies were published between 2003 and 2022. In reducing sBP, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), inorganic nitrates, tart cherry juice, and vitamin D supplementation were more effective than placebo, and the effect of tart cherry juice outranked that of vitamin D, vitamin E, and vitamin K2. In reducing dBP, inorganic nitrates, DHA and EPA, protein, resveratrol, and vitamin D supplementation were more effective than placebo, and the effect of resveratrol outranked that of tart cherry juice, vitamin D, vitamin E, and vitamin K2. However, the effects of tart cherry juice on sBP and resveratrol on dPB were smaller than the pooled effect of placebo, and none of the pairwise differences between the effects of examined supplements were statistically significant. Caution is needed when interpreting these results given concerns about the risk of bias assessed in seven of the twelve studies included in this analysis.

Time course of human skeletal muscle nitrate and nitrite concentration changes following dietary nitrate ingestion.

Dietary nitrate (NO3-) ingestion can be beneficial for health and exercise performance. Recently, based on animal and limited human studies, a skeletal muscle NO3- reservoir has been suggested to be important in whole body nitric oxide (NO) homeostasis. The purpose of this study was to determine the time course of changes in human skeletal muscle NO3- concentration ([NO3-]) following the ingestion of dietary NO3-. Sixteen participants were allocated to either an experimental group (NIT: n = 11) which consumed a bolus of ∼1300 mg (12.8 mmol) potassium nitrate (KNO3), or a placebo group (PLA: n = 5) which consumed a bolus of potassium chloride (KCl). Biological samples (muscle (vastus lateralis), blood, saliva and urine) were collected shortly before NIT or PLA ingestion and at intervals over the course of the subsequent 24 h. At baseline, no differences were observed for muscle [NO3-] and [NO2-] between NIT and PLA (P > 0.05). In PLA, there were no changes in muscle [NO3-] or [NO2-] over time. In NIT, muscle [NO3-] was significantly elevated above baseline (54 ± 29 nmol/g) at 0.5 h, reached a peak at 3 h (181 ± 128 nmol/g), and was not different to baseline from 9 h onwards (P > 0.05). Muscle [NO2-] did not change significantly over time. Following ingestion of a bolus of dietary NO3-, skeletal muscle [NO3-] increases rapidly, reaches a peak at ∼3 h and subsequently declines towards baseline values. Following dietary NO3- ingestion, human m. vastus lateralis [NO3-] expressed a slightly delayed pharmacokinetic profile compared to plasma [NO3-].

Acceptability and Feasibility of a 13-Week Pilot Randomised Controlled Trial Testing the Effects of Incremental Doses of Beetroot Juice in Overweight and Obese Older Adults.

Nitrate-rich food can increase nitric oxide production and improve vascular and brain functions. This study examines the feasibility of a randomised controlled trial (RCT) testing the effects of prolonged consumption of different doses of dietary nitrate (NO3-) in the form of beetroot juice (BJ) in overweight and obese older participants. A single-blind, four-arm parallel pilot RCT was conducted in 62 overweight and obese (30.4 ± 4 kg/m2) older participants (mean ± standard deviation (SD), 66 ± 4 years). Participants were randomized to: (1) high-NO3- (HN: 2 × 70 mL BJ/day) (2) medium-NO3- (MN: 70 mL BJ/day), (3) low-NO3- (LN: 70 mL BJ on alternate days) or (4) Placebo (PL: 70 mL of NO3--depleted BJ on alternate days), for 13 weeks. Compliance was checked by a daily log of consumed BJ, NO3- intake, and by measuring NO3- and NO2- concentrations in plasma, saliva, and urine samples. Fifty participants completed the study. Self-reported compliance to the interventions was >90%. There were significant positive linear relationships between NO3- dose and the increase in plasma and urinary NO3- concentration (R2 = 0.71, P < 0.001 and R2 = 0.46 P < 0.001, respectively), but relationships between NO3- dose and changes in salivary NO3- and NO2- were non-linear (R2 = 0.35, P = 0.002 and R2 = 0.23, P = 0.007, respectively). The results confirm the feasibility of prolonged BJ supplementation in older overweight and obese adults.

The Effects of Beetroot Juice on Blood Pressure, Microvascular Function and Large-Vessel Endothelial Function: A Randomized, Double-Blind, Placebo-Controlled Pilot Study in Healthy Older Adults.

: Dietary nitrate (NO3-) has been reported to improve endothelial function (EF) and blood pressure (BP). However, most studies only assess large-vessel EF with little research on the microvasculature. Thus, the aim of the present pilot study is to examine NO3- supplementation on microvascular and large-vessel EF and BP. Twenty older adults (63 ± 6 years) were randomized to a beetroot juice (BRJ) or placebo (PLA) group for 28 (±7) days and attended three laboratory visitations. Across visitations, blood pressure, microvascular function and large-vessel EF were assessed by laser Doppler imaging (LDI) with iontophoresis of vasoactive substances and flow-mediated dilatation (FMD), respectively. Plasma NO3-concentrations, BP and the presence of NO3- reducing bacteria were also assessed. Plasma NO3- increased following two weeks of BRJ supplementation (p = 0.04) along with a concomitant decrease in systolic and diastolic BP of approximately -6 mmHg and -4 mmHg, respectively (p = 0.04; p = 0.01, respectively). BP remained unchanged in the PLA group. There were no significant differences in endothelium-dependent or endothelium-independent microvascular responses between groups. FMD increased by 1.5% following two weeks of BRJ (p = 0.04), with only a minimal (0.1%) change for the PLA group. In conclusion, this pilot study demonstrated that medium-term BRJ ingestion potentially improves SBP, DBP and large-vessel EF in healthy older adults. The improvements observed in the present study are likely to be greater in populations presenting with endothelial dysfunction. Thus, further prospective studies are warranted in individuals at greater risk for cardiovascular disease.

The Effect of Dietary Nitrate Supplementation on Endurance Exercise Performance in Healthy Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent research into the use of dietary nitrates and their role in vascular function has led to it becoming progressively more popular amongst athletes attempting to enhance performance. OBJECTIVE: The objective of this review was to perform a systematic review and meta-analysis of the literature to evaluate the effect of dietary nitrate (NO3-) supplementation on endurance exercise performance. An additional aim was to determine whether the performance outcomes are affected by potential moderator variables. DATA SOURCES: Relevant databases such as Cochrane Library, Embase, PubMed, Ovid, Scopus and Web of Science were searched for the following search terms 'nitrates OR nitrate OR beetroot OR table beet OR garden beet OR red beet AND exercise AND performance' from inception to October 2015. STUDY SELECTION: Studies were included if a placebo versus dietary nitrate-only supplementation protocol was able to be compared, and if a quantifiable measure of exercise performance was ≥30 s (for a single bout of exercise or the combined total for multiple bouts). STUDY APPRAISAL AND SYNTHESIS: The literature search identified 1038 studies, with 47 (76 trials) meeting the inclusion criteria. Data from the 76 trials were extracted for inclusion in the meta-analysis. A fixed-effects meta-analysis was conducted for time trial (TT) (n = 28), time to exhaustion (TTE) (n = 22) and graded-exercise test (GXT) (n = 8) protocols. Univariate meta-regression was used to assess potential moderator variables (exercise type, dose duration, NO3- type, study quality, fitness level and percentage nitrite change). RESULTS: Pooled analysis identified a trivial but non-significant effect in favour of dietary NO3- supplementation [effect size (ES) = -0.10, 95 % Cl = -0.27 to 0.06, p > 0.05]. TTE trials had a small to moderate statistically significant effect in favour of dietary NO3- supplementation (ES = 0.33, 95 % Cl = 0.15-0.50, p < 0.01). GXT trials had a small but non-significant effect in favour of dietary NO3- supplementation in GXT performance measures (ES = 0.25, 95 % Cl = -0.06 to 0.56, p > 0.05). No significant heterogeneity was detected in the meta-analysis. No statistically significant effects were observed from the meta-regression analysis. CONCLUSION: Dietary NO3- supplementation is likely to elicit a positive outcome when testing endurance exercise capacity, whereas dietary NO3- supplementation is less likely to be effective for time-trial performance. Further work is needed to understand the optimal dosing strategies, which population is most likely to benefit, and under which conditions dietary nitrates are likely to be most effective for performance.