The pilot study was set up to assess whether the used dosing regimen of beetroot juice demonstrated to reach the therapeutic objective. The study was terminated early, as the deadline for the grant application for a larger study was approaching.

The BEET IT study investigates the possible protective effect of beetroot juice on POI following colorectal surgery in (partially) blinded single-center phase 2 randomized trial (pilot study).

Postoperative ileus (POI) is a transient impairment of gastrointestinal motility following abdominal surgery, which leads to increased morbidity, prolonged hospitalization and increased healthcare cost. The pathogenesis of POI involves inflammation and oxidative stress, similar to ischemia/reperfusion injury that can be counteracted with beetroot juice. Beetroot juice is a source of inorganic nitrate, which by conversion of nitrate to nitrite in the body, exerts its protective effect. We before demonstrated in a preclinical model that administration of exogenous nitrite was shown to protect against POI. The aim of this pilot study is to investigate the possible protective effect of beetroot juice ingestion on POI following colorectal surgery.

Inclusion Criteria:

• All patients undergoing colonic or upper rectum laparoscopic surgery.

Exclusion Criteria:

• Pregnancy or breast feeding
• Psychiatric pathology capable of affecting comprehension and judgment faculty
• History of metastatic disease
• History of prior abdominal bowel surgery
• Abdominal radiation treatment
• Chronic constipation (defined as two or fewer bowel movements per week)
• Gut motility influencing agents (e.g. tricyclic antidepressants, chronic use of laxatives)
• Frequent use of mouthwash, as this affects the enterosalivary circulation of nitrate
• Current use of broad-spectrum antibiotics, which will affect the oral flora and likely affect the nitrate reductase activity
• More than one bowel anastomosis during this surgery

Patients undergoing colorectal surgery will be randomized (n=10) to receive one week daily 70 ml of beetroot juice (~ 7 mmol inorganic nitrate) or (n=10) an equivalent volume of nitrate-depleted beetroot juice (control group 1). An additional control group (n=10) is added to the pilot study, in which patients will receive an equivalent volume of water (control group 2); this allows us to investigate whether the antioxidants present in beetroot juice contribute to the protective effect of beetroot juice in POI. Beetroot juice and nitrate-depleted beetroot juice cause discoloration of urine (beeturia) and feces from the purple betacyanin pigments in beetroot; for the control group that receives water, this will not be the case and blinding for this group is thus not possible.