Dietary nitrate and population health: a narrative review of the translational potential of existing laboratory studies

Abstract

Background Dietary inorganic nitrate (NO3−) is a polyatomic ion, which is present in large quantities in green leafy vegetables and beetroot, and has attracted considerable attention in recent years as a potential health-promoting dietary compound. Numerous small, well-controlled laboratory studies have reported beneficial health effects of inorganic NO3− consumption on blood pressure, endothelial function, cerebrovascular blood flow, cognitive function, and exercise performance. Translating the findings from small laboratory studies into ‘real-world’ applications requires careful consideration. Main body This article provides a brief overview of the existing empirical evidence basis for the purported health-promoting effects of dietary NO3− consumption. Key areas for future research are then proposed to evaluate whether promising findings observed in small animal and human laboratory studies can effectively translate into clinically relevant improvements in population health. These proposals include: 1) conducting large-scale, longer duration trials with hard clinical endpoints (e.g. cardiovascular disease incidence); 2) exploring the feasibility and acceptability of different strategies to facilitate a prolonged increase in dietary NO3− intake; 3) exploitation of existing cohort studies to explore associations between NO3− intake and health outcomes, a research approach allowing larger samples sizes and longer duration follow up than is feasible in randomised controlled trials; 4) identifying factors which might account for individual differences in the response to inorganic NO3− (e.g. sex, genetics, habitual diet) and could assist with targeted/personalised nutritional interventions; 5) exploring the influence of oral health and medication on the therapeutic potential of NO3− supplementation; and 6) examining potential risk of adverse events with long term high- NO3− diets. Conclusion The salutary effects of dietary NO3− are well established in small, well-controlled laboratory studies. Much less is known about the feasibility and efficacy of long-term dietary NO3− enrichment for promoting health, and the factors which might explain the variable responsiveness to dietary NO3− supplementation between individuals. Future research focussing on the translation of laboratory data will provide valuable insight into the potential applications of dietary NO3− supplementation to improve population health.

Dietary Inorganic Nitrate as an Ergogenic Aid: An Expert Consensus Derived via the Modified Delphi Technique

“…Health status: The expert panel agreed that chronic dietary nitrate supplementation was ergogenic in healthy individuals, but did not reach consensus for acute supplementation being ergogenic in this population. The expert panel also felt that there was insufficient evidence, or were unable to reach consensus, for acute or chronic dietary nitrate supplementation being ergogenic in clinical populations, which is consistent with the mixed findings reported in the current literature for these cohorts (for a review, see [ 71 ]). It is important to highlight that only 58% of the expert panel reported having experience of using dietary nitrate with clinical populations, compared with 100% of the panel having experience with healthy or sporting populations.…”

“…Although these changes in the oral microbiome composition occurred alongside marked increases in NO biomarkers, it is important to note that the net oral nitrite production is influenced by a complex interplay between various nitrate- and nitrite-reducing microorganisms in the oral cavity. The influence of chronic dietary nitrate consumption on nitrate-reduction capacity of the oral microbial community in response to acute nitrate ingestion, and the impact of potential changes in relation to health and exercise performance, requires further exploration [ 71 ]. One recent study has shown positive associations between oral nitrate-reducing capacity and markers of aerobic fitness [ 80 ].…”

“…Similarly, they agreed that chronic dietary nitrate supplementation in dosages up to ~ 16 mmol/day does not increase risk of methaemoglobinaemia or hypotension. However, given that few studies have explored the long-term health (or other) effects of nitrate, additional well-controlled longitudinal studies are required to support these views [ 71 ]. A consensus was not reached for whether chronic supplementation increases risk of cancer or renal injury, the former of which has been a subject of much debate in the extant literature [ 71 ].…”

Dietary nitrate and brain health. Too much ado about nothing or a solution for dementia prevention?

“…Dietary nitrate therefore has the mechanistic potential to influence brain functions; however, observational and clinical trials, overall, have contrasting results (19,49) . A meta-analysis conducted in 2018 exploring the effects of dietary nitrate supplementation on cognition and CBF (19) found a lack of evidence for the benefits of dietary nitrate on both outcomes.…”

Plasma Nitrate and Nitrite Kinetics after Single Intake of Beetroot Juice in Adult Patients on Chronic Hemodialysis and in Healthy Volunteers: A Randomized, Single-Blind, Placebo-Controlled, Crossover Study

“…During the last decade, there has been an increased interest in investigating the health aspects of dietary nitrate supplementation (aimed to increase NO bioactivity) with a particular focus on cardiovascular regulation and exercise performance [3,4,11,12]. With this in mind, we previously hypothesized that dietary nitrate supplementation may be of benefit in boosting the activity of the nitrate-nitrite-NO pathway, thus restoring NO bioactivity in adult HD patients [10].…”