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

Henrohn, Dan; Björkstrand, Kristoffer; Lundberg, Jon O.; Granstam, Sven-Olof; Baron, Tomasz; Ingimarsdóttir, Inga Jóna; Hedenström, Hans; Malinovschi, Andreï; Wernroth, Mona-Lisa; Jansson, Martin; Hedeland, Mikael; Wikström, Gerhard

doi:10.1016/j.cardfail.2018.09.010

Cited by 24 publications

(22 citation statements)

References 61 publications

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“…In a pilot crossover study in 15 patients with PAH, randomized to two 7-day treatment periods (16 mmol/day nitrate vs. placebo), ingestion of a fixed dose of dietary nitrate was associated with increases in exhaled •NO and plasma and salivary NOx and was not associated with any adverse systemic hemodynamic changes. There were no significant changes in pulmonary hemodynamic parameters assessed by echocardiography or cardiopulmonary exercise testing, or of function tests, such as the 6-minute walk test, although there were trends for improvements in right ventricular function and peak power per liter oxygen consumed, particularly in those patients in whom plasma nitrite flux was .30% postnitrate ingestion (Henrohn et al, 2018). Although these data are encouraging, it remains for larger, adequately powered trials to determine whether inorganic nitrate supplementation has benefit in PAH, with or without other drugs that modulate the •NO-GC-1-cGMP system.…”

Section: Nitrite and Nitrate In The Respiratory Systemmentioning

confidence: 83%

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

Kapil

Khambata

Jones

et al. 2020

Pharmacological Reviews

165

137

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Section: Nitrite and Nitrate In The Respiratory Systemmentioning

confidence: 83%

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

Kapil

Khambata

Jones

et al. 2020

Pharmacological Reviews

165

137

View full text Add to dashboard Cite

“…Other effects of the NO pathway demonstrated by clinical studies are enhancement of blood flow and inhibition of platelet aggregation, therefore possibly protecting BRJ-consumers against cardiovascular disease [13,14]. Additionally, studies have suggested that the NO pathway may be a therapeutic target in patients with pulmonary arterial hypertension [15].…”

Section: Discussionmentioning

confidence: 99%

Consumption of Nitrate-Rich Beetroot Juice with or without Vitamin C Supplementation Increases the Excretion of Urinary Nitrate, Nitrite, and N-nitroso Compounds in Humans

Berends

Berg

Guggeis

et al. 2019

IJMS

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Consumption of nitrate-rich beetroot juice (BRJ) by athletes induces a number of beneficial physiological health effects, which are linked to the formation of nitric oxide (NO) from nitrate. However, following a secondary pathway, NO may also lead to the formation of N-nitroso compounds (NOCs), which are known to be carcinogenic in 39 animal species. The extent of the formation of NOCs is modulated by various other dietary factors, such as vitamin C. The present study investigates the endogenous formation of NOCs after BRJ intake and the impact of vitamin C on urinary NOC excretion. In a randomized, controlled trial, 29 healthy recreationally active volunteers ingested BRJ with or without additional vitamin C supplements for one week. A significant increase of urinary apparent total N-nitroso Compounds (ATNC) was found after one dose (5 to 47 nmol/mmol: p < 0.0001) and a further increase was found after seven consecutive doses of BRJ (104 nmol/mmol: p < 0.0001). Vitamin C supplementation inhibited ATNC increase after one dose (16 compared to 72 nmol/mmol, p < 0.01), but not after seven daily doses. This is the first study that shows that BRJ supplementation leads to an increase in formation of potentially carcinogenic NOCs. In order to protect athlete’s health, it is therefore important to be cautious with chronic use of BRJ to enhance sports performances.

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“…7 The immediate effects of the multi-component formula were rather surprising, as dietary nitrate requires at least an hour to show any known biological effects in humans, with the peak effect usually reported after 180 minutes. [4][5][6] In addition, this nitrate-based nutritional formula appears to be comparable to conventional therapy in treating low SpO 2 caused by COVID-19. The increase in oxygen concentrations seen in patients with COVID-19 on oxygen therapy (1-6 L/ minute) was approximately 4% with each liter of O 2 per minute, 8 which is similar to findings reported in our trial (mean SpO 2 increase ¼ 3.6%).…”

mentioning

confidence: 89%

Oxygen saturation improved with nitrate-based nutritional formula in patients with COVID-19

et al. 2021

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In this open-label case series trial, we evaluated the effects of a nitrate-based nutritional formula on oxygen saturation (SpO2) and patient-reported outcomes in individuals with coronavirus disease 2019 (COVID-19). Five adult patients (three men and two women, age 39.6 ± 6.9 years) with a positive COVID-19 test result, breathing difficulties, and SpO2 ≤95%, who were free from other pulmonary and cardiovascular conditions, were recruited for this study. Participants were assigned to receive a multi-component nutritional formula (containing 1200 mg of potassium nitrate, 200 mg of magnesium, 50 mg of zinc, and 1000 mg of citric acid) every 4 hours during the 48-hour monitoring period. In all participants, SpO2 improved immediately after administration of the nutritional formula, from 1 to 7 percentage points (mean increase 3.6 ± 2.7 points; 95% confidence interval 0.3 to 7.0). SpO2 remained above baseline values throughout the monitoring interval, with values persisting over threshold values (>92%) for all patients and at each time point during the 48 hours. No patients reported any side effects of the intervention. These promising and rather unexpected results call for immediate, well-sampled, mechanistic randomized controlled trials to validate our findings.

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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

Cited by 24 publications

References 61 publications

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

The Noncanonical Pathway for In Vivo Nitric Oxide Generation: The Nitrate-Nitrite-Nitric Oxide Pathway

Consumption of Nitrate-Rich Beetroot Juice with or without Vitamin C Supplementation Increases the Excretion of Urinary Nitrate, Nitrite, and N-nitroso Compounds in Humans

Oxygen saturation improved with nitrate-based nutritional formula in patients with COVID-19

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