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Am J Clin Nutr. 2018 Apr 1;107(4):504-522. doi: 10.1093/ajcn/nqx046.

Nitrate, the oral microbiome, and cardiovascular health: a systematic literature review of human and animal studies.

Author information

1
Medical School, Royal Perth Hospital Unit, University of Western Australia, Perth, Western Australia, Australia.
2
School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, Australia.
3
School of Biomedical Sciences and Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.
4
Medical School, Queen Elizabeth Medical Center Unit, University of Western Australia, Nedlands, Western Australia, Australia.

Abstract

Background:

Dietary nitrate is an important source of nitric oxide (NO), a molecule critical for cardiovascular health. Nitrate is sequentially reduced to NO through an enterosalivary nitrate-nitrite-NO pathway that involves the oral microbiome. This pathway is considered an important adjunct pathway to the classical l-arginine-NO synthase pathway.

Objective:

The objective of this study was to systematically assess the evidence for dietary nitrate intake and improved cardiovascular health from both human and animal studies.

Design:

A systematic literature search was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines by using key search terms in Medline and EMBASE databases and defined inclusion and exclusion criteria.

Results:

Thirty-seven articles on humans and 14 articles on animals were included from 12,541 screened references. Data on the effects of dietary nitrate on blood pressure, endothelial function, ischemic reperfusion injury, arterial stiffness, platelet function, and cerebral blood flow in both human and animal models were identified. Beneficial effects of nitrate on vascular health have predominantly been observed in healthy human populations, whereas effects in populations at risk of cardiovascular disease are less clear. Few studies have investigated the long-term effects of dietary nitrate on cardiovascular disease clinical endpoints. In animal studies, there is evidence that nitrate improves blood pressure and endothelial function, particularly in animal models with reduced NO bioavailability. Nitrate dose seems to be a critical factor because there is evidence of cross-talk between the 2 pathways of NO production.

Conclusions:

Evidence for a beneficial effect in humans at risk of cardiovascular disease is limited. Furthermore, there is a need to investigate the long-term effects of dietary nitrate on cardiovascular disease clinical endpoints. Further animal studies are required to elucidate the mechanisms behind the observed effects.

PMID:
29635489
DOI:
10.1093/ajcn/nqx046
[Indexed for MEDLINE]

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