Author + information
- Received October 26, 2015
- Revision received December 14, 2015
- Accepted December 17, 2015
- Published online June 1, 2016.
- Joel Eggebeen, MSa,
- Daniel B. Kim-Shapiro, PhDb,c,∗∗ (, )
- Mark Haykowsky, PhDd,
- Timothy M. Morgan, PhDe,
- Swati Basu, PhDb,c,
- Peter Brubaker, PhDc,f,
- Jack Rejeski, PhDc,f and
- Dalane W. Kitzman, MDa,c,∗ ()
- aSections of Cardiovascular Medicine and Geriatrics, Wake Forest School of Medicine, Winston-Salem, North Carolina
- bDepartment of Physics, Wake Forest University, Winston-Salem, North Carolina
- cTranslational Science Center, Wake Forest University, Winston-Salem, North Carolina
- dCollege of Nursing and Health Innovation, University of Texas at Arlington, Arlington, Texas
- eDepartment of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina
- fHealth and Exercise Science Department, Wake Forest University, Winston-Salem, North Carolina
- ↵∗Reprint requests and correspondence:
Dr. Dalane W. Kitzman, Section of Cardiovascular Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157.
- ↵∗∗Dr. Daniel B. Kim-Shapiro, Department of Physics, Wake Forest University, Winston-Salem, North Carolina 27109.
Objectives This study sought to determine whether a relatively low single dose or a week-long dosage of dietary inorganic nitrate could improve exercise tolerance in patients with heart failure with preserved ejection fraction (HFpEF).
Background Exercise intolerance is the primary manifestation of HFpEF and is largely due to noncardiac factors that reduce oxygen delivery to active skeletal muscles. A recent study showed improved exercise capacity in patients with HFpEF after a single, acute dose of beetroot juice (BRJ) (12.9 mmol inorganic nitrate) while another recent study showed neutral and negative effects of an organic nitrate.
Methods Twenty HFpEF patients (69 ± 7 years of age ) were enrolled in an initial cross-over design comparing a single, acute dose of BRJ (6.1 mmol nitrate) to a nitrate-depleted placebo BRJ. A second phase, 1 week of daily doses, used an all-treated design in which patients consumed BRJ for an average of 7 days. The primary outcome of the study was submaximal aerobic endurance, measured as cycling time to exhaustion at 75% of measured maximal power output.
Results No adverse events were associated with the intervention. Submaximal aerobic endurance improved 24% after 1 week of daily BRJ dosing (p = 0.02) but was not affected by the single, acute dose of the BRJ compared to placebo. Consumption of BRJ significantly reduced resting systolic blood pressure and increased plasma nitrate and nitrite in both of the dosing schemes.
Conclusions One week of daily dosing with BRJ (6.1 mmol inorganic nitrate) significantly improves submaximal aerobic endurance and blood pressure in elderly HFpEF patients.
This work was supported by National Institutes of Health grants R01AG18915, R01AG045551, P30AG021332, and HL058091; the Kermit Glenn Phillips II Chair in Cardiovascular Medicine, Wake Forest School of Medicine; the Moritz Chair in Geriatrics, College of Nursing and Health Innovation, University of Texas at Arlington; and the Translational Science Center, Reynolda Campus, Wake Forest University. Dr. Kim-Shapiro is co-inventor on a patent related to the use of nitrite under cardiovascular conditions, and owns stock in and serves on the scientific advisory board for Beverage Operations LLC, which has licensed Wake Forest University intellectual properties and thus has a financial interest in Beverage Operations LLC. Dr. Kitzman is a consultant for Abbvie, GlazoSmithKline, Relypsa, Regeneron, Merck, Corvia Medical, and Actavis; has received grants from Novartis; and owns stock in Gilead Sciences and Relypsa. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received October 26, 2015.
- Revision received December 14, 2015.
- Accepted December 17, 2015.
- American College of Cardiology Foundation