Does dietary nitrate supplementation improve performance in cardiopulmonary exercise testing and post-operative recoveryin patients with colorectal cancer? A randomised controlled trial

Abstract

Major surgery generates a stress response which increases oxygen demand and consumption post-operatively. Patients with low cardiopulmonary reserve may not be able to meet the increased oxygen demand and are at risk of increased morbidity. Dietary nitrate reduces the amount of oxygen required to perform a set amount of exercise and enhances exercise tolerance and performance in athletes by improving oxygen utilisation. Cardiopulmonary exercise testing (CPX) is an established method of assessing patients’ cardiopulmonary reserve prior to surgery. The anaerobic threshold (AT) is the oxygen uptake at which anaerobic metabolism supplements aerobic metabolism; is calculated during CPX and can predict short and long term outcomes after surgery and postoperative complications. We conducted a single centre, randomised, double-blind, placebo controlled trial to determine if dietary organic nitrate supplementation with beetroot juice (BRJ) improves pre-operative performance in CPX in patients with colorectal cancer (CRC). Eligible patients were adults undergoing elective laparoscopic resection for CRC. Patients were randomised to receive BRJ or nitrate-depleted BRJ (Placebo). Initial CPX was performed to a standard ramped incremental exercise protocol. Patients then received BRJ or placebo every day for 7 days followed by a second CPX. The primary outcome measure was the change in AT. There was a statistically significant increase in the mean AT in the nitrate group (+0.706, 95% CI 0.130 to 1.281; p=0.018) but not in the placebo group. There was a significantly lower length of stay in nitrates group. There was no significant difference in rate of complications between the two groups. Just 7 days of dietary nitrate supplementation results in a significant improvement in oxygen utilisation in an elderly population with colorectal cancer. This is a novel finding and this study is the first in patients undergoing surgery. This trial provides evidence that dietary nitrate supplementation is beneficial in a preoperative setting.