Effects of Dietary Nitrate Supplementation on Cardiorespiratory Control in Chronic Heart Failure

Dietary Nitrate Supplementation and Cardiorespiratory Control in Chronic Heart Failure: a Randomized, Placebo-controlled Trial

The main purpose of this study is to determine whether dietary nitrate supplementation via concentrated beetroot juice improves central and peripheral cardiovascular control and physical capacity in patients with systolic heart failure.

Chronic heart failure (CHF) is a leading cause of morbidity and mortality worldwide. Although affecting the heart at first, it is now recognized that disability is largely due to impaired cerebral and skeletal muscle blood flow and consequently microvascular oxygenation. Reduced muscle oxygenation compromises oxidative metabolism and thus contractile performance. Impaired cerebral oxygenation not only reduces motor output (thus exacerbating muscle fatigue) but also constitutes a predictor of cerebral ischemic events and an independent prognostic risk factor. Reduced levels of the vasodilator nitric oxide (NO) contribute to impaired blood flow and oxygenation in CHF. Development of new effective therapeutic strategies is therefore crucial given that current pharmacological treatment has failed to abrogate oxygenation deficits in CHF patients. Emerging evidence shows that nitrate serves as an alternative source for NO and improves muscle blood flow and oxygenation in health. Another striking feature of nitrate is that it can improve muscle work efficiency, a tenet of physiology that was once considered immutable. Objective: To investigate systematically the role of dietary nitrate supplementation on central and peripheral cardiovascular function in CHF patients.

Nitrate supplementation: concentrated nitrate-rich beetroot juice (2 x 70 ml/day; approximately 10 mmol nitrate/day; Beet It, James White Drinks, Ipswich, UK) for 8 consecutive days.

Placebo: nitrate-depleted beetroot juice (2 x 70 ml/day; approximately 0.01 mmol nitrate/day; Beet It, James White Drinks, Ipswich, UK) for 8 consecutive days. The placebo juice is similar to the concentrated beetroot juice in appearance, texture, smell and taste and is obtained by removing nitrate ions from the latter.

Assessed by near-infrared spectroscopy and the rate of appearance of the optically-dense indocyanine green dye

Non-invasive evaluation of cardiac (mean arterial pressure, cardiac output, stroke volume and heart rate) and pulmonary gas exchange (e.g., minute ventilation and oxygen uptake) responses during the transition from rest to exercise

Inclusion Criteria: - previous diagnosis of systolic heart failure (left ventricular ejection fraction <40%) under optimized clinical treatment as judged by the accompanying physician. Exclusion Criteria: hospital admission in the previous 6 weeks; exercise training program in the previous 6 months; nitrate therapy (e.g., isosorbide dinitrate); tabagism; any condition that could interfere with the ability to exercise; diagnosed psychiatric or cognitive disorders; type I insulin-dependent diabetes mellitus; excessively over-weight (BMI>35kg/m²); other diagnosed cardiorespiratory disorders (e.g., chronic obstructive pulmonary disease, peripheral artery disease).