By Concepta Merry, MB, BCh, BAO, BA
Associate Professor, Global Health, School of Medicine, Trinity College Dublin
Dr. Merry reports no financial relationships relevant to this field of study.
SUMMARY POINTS
- This study examined the effect of beetroot juice consumption in 20 patients with heart failure and preserved ejection fraction.
- It is thought that beetroot exerts an effect by being a source of inorganic nitrates, feeding into nitric oxide physiology.
- One week of daily beetroot juice providing 0.38 grams of inorganic nitrates improved submaximal aerobic endurance more than in people randomized to a matching placebo juice.
SYNOPSIS: Researchers found that drinking beetroot juice daily improves submaximal aerobic endurance in patients with cardiac failure and preserved ejection fraction.
SOURCE: Eggebeen J, Kim-Shapiro DB, Haykowsky M, et al. One week of daily dosing with beetroot juice improves submaximal endurance and blood pressure in older patients with heart failure and preserved ejection fraction. JACC Heart Fail 2016;4:428-437.
Beetroot juice is a rich source of inorganic nitrate. Inorganic nitrates release nitric oxide slowly to skeletal muscle, which makes beetroot juice a potential candidate for the submaximal aerobic endurance in heart failure patients with preserved ejection fraction. Eggebeen et al compared once-off acute dosing vs. one-week daily dosing with beetroot juice and found that one week of daily beetroot juice supplementation was well tolerated and improved submaximal aerobic endurance in heart failure patients with preserved ejection fraction.
Although some assume that heart failure is synonymous with reduced ejection fraction, heart failure with preserved ejection fraction is actually the most common form of heart failure.1,2 Exercise intolerance is the cardinal clinical feature of this particular form of heart failure.3 One key factor responsible for low exercise tolerance seen in elderly people with heart failure and preserved ejection fraction is thought to be low levels of the vasodilator nitric oxide.4 This raises the possibility that, theoretically, nitric oxide supplementation could help people with heart failure and preserved ejection fraction.
Essentially, there are two main sources of nitric oxide — organic and inorganic. Organic nitrates, which include compounds such as nitroglycerin and isosorbide mononitrate, release large amounts of nitric oxide but do not affect exercise tolerability in heart failure patients with preserved ejection fraction.5
Beetroot juice is a rich source of inorganic nitrates, and some (but not all) studies have shown that beetroot juice supplementation can improve exercise performance in young healthy patients.6,7,8 Inorganic nitrates differ from organic nitrates in that they release nitric oxide more slowly, resulting in more sustained concentrations of nitric oxide at target areas of low oxygen, such as skeletal muscle, during exercise.9 Other sources of inorganic nitrate include arugula and spinach.
Clinical data show that a single dose of beetroot juice increased work performance and cardiac output but did not affect exercise efficiency (total work/total oxygen consumed).10 Beetroot juice may be a plausible candidate for helping elderly patients with cardiac failure and preserved ejection fraction, but there is still work to be done to better understand how best to use beetroot juice. Specifically, it is important to evaluate different dosing strategies, given that some studies showed benefits with daily dosing that were not seen with a single one-off dose.10,11,12
Eggebeen et al assessed whether one week of daily dosing with beetroot juice would be superior to a single dose of beetroot juice in terms of improving submaximal aerobic endurance in heart failure patients with preserved ejection fraction. This NIH-sponsored study was conducted in North Carolina. Of note, one investigator reported a potential financial conflict of interest in relation to both the brand of beetroot juice used and to a positive outcome of the study.
Heart failure with preserved ejection fraction was defined as a heart failure clinical score of ≥ 3, according to the American College of Cardiology Foundation/American Heart Association, with a preserved ejection fraction ≥ 50%. Inclusion criteria for entry into the study was a diagnosis of heart failure with preserved ejection fraction plus exercise intolerance. Exclusion criteria included significant valvular or ischemic heart disease or any other concomitant disorder that could contribute to the patient’s symptoms, as well as use of nitrate medication, phosphodiesterase type 5 inhibitors, or any medication used to alter the pH of the stomach. The authors screened 252 patients from a database of previous related studies, and 57 patients were identified as possible study subjects. Ultimately, 20 patients met the eligibility criteria for inclusion in the study.
The participants were randomized to receive either beetroot juice or a matching placebo. The beetroot juice contained 0.38 grams (6.1 millimoles) of inorganic nitrate, while the placebo contained 0.0003 grams (4.8 micromole) of inorganic nitrate. Every effort was made to ensure that the placebo matched the beetroot juice with the exception of the nitric oxide concentration. The beetroot juice manufacturer removed the beetroot to make the matching placebo juice.
The study design was described as a double-blind, randomized, crossover trial, but it actually was more complex. The study had two different phases. Phase 1 was the crossover, randomized phase of the study, in which patients were randomized to either receive beetroot juice or placebo. Patients acted as their own controls and took either beetroot juice or placebo juice as a single acute dose, followed by a washout period of three to seven days. They then took the single acute dose of the crossover product. In Phase 2, after completing the single acute crossover part of the study, study participants then consumed one bottle (70 mL) of beetroot juice daily for one week. Study patients did not know whether they were consuming beetroot juice or placebo during the week-long beetroot juice phase of the study.
The primary outcome of the study was aerobic exercise endurance (time to volitional exhaustion during sub maximal cycling), while secondary outcomes included plasma nitrate, nitrite, and blood pressure measurements over the exercise period. The 20 study participants were predominantly older females, which is representative of the characteristic demographic of patients with heart failure with preserved ejection fraction. Nineteen of 20 patients completed the study, but one participant was excluded from the final analysis because of knee pain, which compromised participation in the exercise tests that were part of the study design. No serious adverse events were reported. Study compliance was measured by the return bottle count.
Submaximal aerobic exercise endurance improved with one week of daily dosing (beetroot juice: 449 ± 180 s vs. placebo 363 ± 125 s: 24% increase; P = 0.02). However, no differences were noted for the primary outcome with single acute dosing of beetroot juice (beetroot juice: 352 ± 116 s vs. placebo: 377 ± 134 s; P = 0.47).
Both the once-off acute dose and one week of daily dosing of beetroot juice significantly increased plasma nitric oxide concentrations by 138% and 129%, respectively, compared to placebo. Single acute dosing plasma resulted in nitrate levels of 362 ± 158 micromole vs. 85 ± 104 micromole (P < 0.001) and nitrite levels of 0.81 ± 0.91 micromole vs. 0.34 ± 0.26 micromole (P = 0.01), which were significantly higher compared to placebo. The one week of daily beetroot schedule resulted in plasma nitrate levels of 461 ± 229 micromole vs. 85 micromole (P < 0.001) and nitrite levels of 0.78 ± 0.52 micromole vs. 0.34 ± 0.26 micromole (P < 0.001) as compared with placebo.
Resting systolic blood pressure was significantly lower compared to placebo in the acute dosing group (127 ± 14 mmHg vs. 134 ± 14 mmHg; P = 0.008) and in the one week of daily dosing (120 ± 13 mmHg vs. 134 ± 14 mmHg; P < 0.001).
In summary, the authors drew three key conclusions from the study findings:
- The beetroot juice supplementation was both feasible and safe.
- One week of daily max doses of beetroot juice improved submaximal aerobic endurance.
- Both single acute dosing and one week of daily dosing reduced resting systolic blood pressure.
From these results, they concluded that one week of daily beetroot juice supplementation could be a potential option to improve submaximal aerobic endurance with a reduction of blood pressure in the growing population of elderly patients with heart failure and preserved ejection fraction.
In another related study, Zamani and colleagues used a higher dose of nitrate of 12.9 millimoles vs. 6.1 millimoles.13 Zamani noted an increase in total work performed after single acute dose of beetroot juice in heart failure patients with ejection fraction. Comparing the results of the Zamani study with this current study, the authors suggested that there may be benefits to both acute and chronic dosing with beetroot juice and suggested the following pragmatic approach to beetroot dosing: Patients could consume beetroot juice at the lower dose to improve everyday activity and quality of life, but could also supplement with additional nitrate as an acute single dose before anticipated activity that may be physically challenging.
The two main study limitations included the small number of participants and the lack of information on the calorie or sugar content of the drink.
COMMENTARY
The authors recommended that larger clinical trials be conducted to determine whether dietary inorganic nitrate can help improve everyday quality of life for patients with heart failure and preserved ejection fraction. This is pretty much the standard recommendation at the end of any clinical paper. However, it is worth further investigating what has been achieved in this dataset from 18 patients. Also, in the future, clinicians could consider the possibility of using natural products as dietary supplements that can be titrated to match the anticipated physical demands of the day.
REFERENCES
- Kitzman DW, Gardin JM, Gottdiener JS, et al. Importance of heart failure with preserved systolic function in patients > or = 65 years of age. CHS Research Group. Cardiovascular Health Study. Am J Cardiol 2001;87:413-419.
- Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 2006;355:251-259.
- Kitzman DW, Little WC, Brubaker PH, et al. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA 2002;288:2144-2150.
- Hirai DM, Musch TI, Poole DC. Exercise training in chronic heart failure: Improving skeletal muscle O2 transport and utilization. Am J Physiol Heart Circ Physiol 2015;309:H1419–H1439.
- Redfield MM, Anstrom KJ, Levine JA, et al. Isosorbide mononitrate in heart failure with preserved ejection fraction. N Engl J Med 2015;373:2314-2324.
- Bailey SJ, Fulford J, Vanhatalo A, et al. Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans. J Appl Physiol 2010;109:135-148.
- Lansley K, Winyard P, Fulford J, et al. Dietary nitrate supplementation reduces the O2 cost of walking and running: A placebo-controlled study. J Appl Physiol 2011;110:591-600.
- Lansley KE, Winyard PG, Bailey SJ, et al. Acute dietary nitrate supplementation improves cycling time trial performance. Med Sci Sports Exerc 2011;43:1125-1131.
- Lundberg JO, Carlstrom M, Larsen FJ, Weitzberg E. Roles of dietary inorganic nitrate in cardiovascular health and disease. Cardiovasc Res 2011;89:525-532.
- Hoon MW, Johnson NA, Chapman PG, Burke LM. The effect of nitrate supplementation on exercise performance in healthy individuals: A systematic review and meta-analysis. Int J Sport Nutr Exerc Metab 2014;23:522-532.
- Cermak N, Gibala MJ, van Loon LJC. Nitrate supplementation’s improvement of 10-km time-trial performance in trained cyclists. Int J Sport Nutr Exer Metab 2012;22:64-71.
- Vanhatalo A, Bailey SJ, Blackwell JR, et al. Acute and chronic effects of dietary nitrate supplementation on blood pressure and the physiological responses to moderate-intensity and incremental exercise. Am J Physiol Regul Integr Comp Physiol 2010;299:R1121-R1131.
- Zamani P, Rawat D, Shiva-Kumar P, et al. Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction. Circulation 2015;131:371-380.
Researchers found that drinking beetroot juice daily improves submaximal aerobic endurance in patients with cardiac failure and preserved ejection fraction.
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