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Inorganic nitrate supplementation may improve diastolic function and the O2 cost of exercise in cancer survivors: a pilot study

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Abstract

In non-cancer populations, inorganic dietary nitrate (NO3−) supplementation is associated with enhanced cardiorespiratory function but remains untested in patients with a history of cancer. Therefore, this pilot study sought to determine if oral NO3− supplementation, as a supportive care strategy, increases left ventricular (LV) function and exercise performance in survivors of cancer treated with anticancer therapy while simultaneously evaluating the feasibility of the methods and procedures required for future large-scale randomized trials. Two cohorts of patients with a history of cancer treated with anticancer chemotherapy were recruited. Patients in cohort 1 (n = 7) completed a randomized, double-blind, crossover study with 7 days of NO3− or placebo (PL) supplementation, with echocardiography. Similarly, patients in cohort 2 (n = 6) received a single, acute dose of NO3− supplementation or PL. Pulmonary oxygen uptake (VO2), arterial blood pressure, and stroke volume were assessed during exercise. In cohort 1, NO3− improved LV strain rate in early filling (mean difference (MD) [95% CI]: − 0.3 1/s [− 0.6 to 0.06]; P = 0.04) and early mitral septal wall annular velocity (MD [95% CI]: 0.1 m/s [− 0.01 to − 0.001]; P = 0.02) compared to placebo. In cohort 2, NO3− decreased the O2 cost of low-intensity steady-state exercise (MD [95% CI]: − 0.5 ml/kg/min [− 0.9 to − 0.09]; P = 0.01). Resting and steady-state arterial blood pressure and stroke volume were not different between conditions. No differences between conditions for peak VO2 (MD [95% CI]: − 0.7 ml/kg/min [− 3.0 to 1.6]; P = 0.23) were observed. The findings from this pilot study warrant further investigation in larger clinical trials targeting the use of long-term inorganic dietary NO3− supplementation as a possible integrative supportive care strategy in patients following anticancer therapy.

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Data availability

Available from the corresponding author on reasonable request.

Code availability

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Abbreviations

BRJ:

Beetroot juice

Q:

Cardiac output

E:

Early mitral valve filling

Ea :

Effective arterial elastance

EDV:

End-diastolic volume

ESV:

End-systolic volume

NO3 − :

Inorganic nitrates

A:

Late mitral valve filling

LV:

Left ventricular

LVEF:

Left ventricular ejection fraction

Ees :

Left ventricular end-systolic elastance

LVOT:

Left ventricular outflow tract

MV:

Mitral valve

NO:

Nitric oxide

Em:

Peak myocardial velocities in early filling

Sm:

Peak myocardial velocities in systole

PL:

Placebo

VO2 :

Pulmonary oxygen uptake

SV:

Stroke volume

SVR:

Systemic vascular resistance

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Author information

Author notes

  1. Vanessa-Rose G. Turpin and Garrett M. Lovoy contributed equally to this work.

Authors and Affiliations

  1. Department of Kinesiology, College of Health and Human Sciences, Kansas State University, Manhattan, USA

    Vanessa-Rose G. Turpin, Garrett M. Lovoy, Shannon K. Parr, Stephen T. Hammond, Hunter K. Post, Jacob T. Caldwell, Heather R. Banister, Britton C. Scheuermann, Trenton D. Colburn & Carl J. Ade

  2. Physician Assistant Studies, College of Health and Human Sciences, Kansas State University, Manhattan, USA

    Carl J. Ade

  3. Johnson Cancer Research Center, Kansas State University, Manhattan, USA

    Carl J. Ade

  4. Clinical Integrative Physiology Laboratory, Kansas State University, Manhattan, KS, 66506, USA

    Carl J. Ade

Authors
  1. Vanessa-Rose G. Turpin
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  2. Garrett M. Lovoy
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Contributions

VRGT, GML, HKP, JTC, and CJA: conceptualization and methodology. VRGT, GML, SKP, STH, HKP, JTC, and HRB: analysis and investigation. VRGT, GML, SKP, STH, HKP, JTC, HRB, BCS, and TDC: writing—original draft preparation, review, and editing. TDC, JTC, and CJA: resources and supervision.

Corresponding author

Correspondence to Carl J. Ade.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained on all individual participants included in the study.

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The authors have no competing interests to declare that are relevant to the content of this article. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The authors have no financial or proprietary interests in any material discussed in this article.

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Turpin, VR.G., Lovoy, G.M., Parr, S.K. et al. Inorganic nitrate supplementation may improve diastolic function and the O2 cost of exercise in cancer survivors: a pilot study. Support Care Cancer 31, 63 (2023). https://doi.org/10.1007/s00520-022-07520-6

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