Format

Send to

Choose Destination
J Card Fail. 2018 Sep 20. pii: S1071-9164(18)31003-0. doi: 10.1016/j.cardfail.2018.09.010. [Epub ahead of print]

Effects of Oral Supplementation With Nitrate-Rich Beetroot Juice in Patients With Pulmonary Arterial Hypertension-Results From BEET-PAH, an Exploratory Randomized, Double-Blind, Placebo-Controlled, Crossover Study.

Author information

1
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden. Electronic address: dan_henrohn@hotmail.com.
2
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
3
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
4
Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
5
Department of Medical Sciences, Cardiology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden; Department of Medical Sciences, Clinical Physiology, Uppsala University, Uppsala University Hospital, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
6
Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
7
Department of Chemistry, Environment and Feed Hygiene, National Veterinary Institute, (SVA), Uppsala, Sweden; Division of Analytical Pharmaceutical Chemistry, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.

Abstract

BACKGROUND:

The nitrate-nitrite-nitric oxide (NO) pathway may represent a potential therapeutic target in patients with pulmonary arterial hypertension (PAH). We explored the effects of dietary nitrate supplementation, with the use of nitrate-rich beetroot juice (BRJ), in patients with PAH.

METHODS AND RESULTS:

We prospectively studied 15 patients with PAH in an exploratory randomized, double-blind, placebo-controlled, crossover trial. The patients received nitrate-rich beetroot juice (∼16 mmol nitrate per day) and placebo in 2 treatment periods of 7 days each. The assessments included; exhaled NO and NO flow-independent parameters (alveolar NO and bronchial NO flux), plasma and salivary nitrate and nitrite, biomarkers and metabolites of the NO-system, N-terminal pro-B-type natriuretic peptide, echocardiography, ergospirometry, diffusing capacity of the lung for carbon monoxide, and the 6-minute walk test. Compared with placebo ingestion of BRJ resulted in increases in; fractional exhaled NO at all flow-rates, alveolar NO concentrations and bronchial NO flux, and plasma and salivary levels of nitrate and nitrite. Plasma ornithine levels decreased and indices of relative arginine availability increased after BRJ compared to placebo. A decrease in breathing frequency was observed during ergospirometry after BRJ. A tendency for an improvement in right ventricular function was observed after ingestion of BRJ. In addition a tendency for an increase in the peak power output to peak oxygen consumption ratio (W peak/VO2 peak) was observed, which became significant in patients reaching an increase of plasma nitrite >30% (responders).

CONCLUSIONS:

BRJ administered for 1 week increases pulmonary NO production and the relative arginine bioavailability in patients with PAH, compared with placebo. An increase in the W peak/VO2 peak ratio was observed after BRJ ingestion in plasma nitrite responders. These findings indicate that supplementation with inorganic nitrate increase NO synthase-independent NO production from the nitrate-nitrite-NO pathway.

KEYWORDS:

Pulmonary arterial hypertension; beetroot juice; nitrate; nitric oxide; nitrite

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center