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A Translational Randomized Trial of Perioperative Arginine Immunonutrition on Natural Killer Cell Function in Colorectal Cancer Surgery Patients

  • Translational Research
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Surgery results in severe impairment of natural killer (NK) cell cytotoxicity (NKC) and activity (NKA, cytokine secretion), and a dramatic drop in arginine levels. Postoperative immunosuppression is associated with increased complications and recurrence. Perioperative arginine is reported to reduce postoperative complications. Because arginine modulates NK cell function, this study aimed to determine whether perioperative consumption of arginine-enriched supplements (AES) can improve NK cell function in colorectal cancer (CRC) surgery patients.

Methods

This study randomized 24 CRC patients to receive the AES or isocaloric/isonitrogenous control supplement three times a day for five days before and after surgery. The AES contained 4.2 g of arginine per dose (12.6 g/day). The primary objective was to determine whether AES improved NKC by 50 % compared with the control group after surgery.

Results

On surgery day (SD) 1, NKC was significantly reduced postoperatively in the control group by 50 % (interquartile range [IQR], 36–55 %; p = 0.02) but not in the AES group (25 % reduction; IQR, 28–75 %; p = 0.3). Furthermore, AES had no benefit in terms of NKA or NK cell number. Compliance was much greater preoperatively (>91 %) than postoperatively (<46 %). However, despite excellent preoperative compliance, arginine was rapidly cleared from the blood within 4 h after consumption and therefore, did not prevent the postoperative drop in arginine.

Conclusions

Oral consumption of arginine immunonutrition resulted in a modest improvement in NKC after surgery but was unable to prevent postoperative arginine depletion or the suppression of NKA (ClinicalTrials.gov NCT02987296).

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Acknowledgment

This work was funded by grants from the Canadian Association of General Surgeons (CAGS), the Cancer Research Society (CRS), the Canadian Institutes of Health Research (CIHR), and The Ottawa Hospital Academic Medical Organization (TOHAMO) Innovation Fund Grant 2015. Trial reagents were provided as in-kind support from ATGen Canada/NKMax and Enhanced Medical Nutrition.

Funding

The immunonutritional interventions and control supplements were provided as in-kind support by Enhanced Medical Nutrition, and ATGen Canada/NKMax provided study materials as in-kind support for measuring NK cell cytokine secretion.

Author information

Authors and Affiliations

  1. Cancer Therapeutics Program, The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

    Leonard Angka PhD, Andre B. Martel MSc, MD, Juliana Ng BSc, Manahil Sadiq BSc, Ahwon Jeong BSc, Marlena Scaffidi BSc, Christiano Tanese de Souza DVM, Michael A. Kennedy PhD & Rebecca C. Auer MSc, MD, FRCSC

  2. Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa, Ontario, Canada

    Leonard Angka PhD, Andre B. Martel MSc, MD & Rebecca C. Auer MSc, MD, FRCSC

  3. Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada

    Andre B. Martel MSc, MD, Shaheer Tadros MD, FRCSC & Rebecca C. Auer MSc, MD, FRCSC

  4. Division of General Surgery, The Ottawa Hospital, Ottawa, Ontario, Canada

    Andre B. Martel MSc, MD, Shaheer Tadros MD, FRCSC & Rebecca C. Auer MSc, MD, FRCSC

  5. Department of Medicine, The Ottawa Hospital, Ottawa, Ontario, Canada

    Amanda Pecarskie BSc

  6. Centre for Infection, Immunity, and Inflammation, University of Ottawa, Ottawa, ON, Canada

    Rebecca C. Auer MSc, MD, FRCSC

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  1. Leonard Angka PhD
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  2. Andre B. Martel MSc, MD
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  3. Juliana Ng BSc
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  7. Marlena Scaffidi BSc
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  11. Rebecca C. Auer MSc, MD, FRCSC
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Contributions

LA, AM, and MK performed the experiments. LA, AM, JN, MS, AJ, MSc, CS, and MK processed and stored the patient blood samples. JN, AP, MS, AJ, MSc were the clinical coordinators who informed and recruited patients for the trial. LA wrote the manuscript with editing help from AM, MK, and RA. ST and RA were the operating surgeons. RA conceived and supervised the study.

Corresponding author

Correspondence to Rebecca C. Auer MSc, MD, FRCSC.

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Angka, L., Martel, A.B., Ng, J. et al. A Translational Randomized Trial of Perioperative Arginine Immunonutrition on Natural Killer Cell Function in Colorectal Cancer Surgery Patients. Ann Surg Oncol 29, 7410–7420 (2022). https://doi.org/10.1245/s10434-022-12202-y

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  • DOI: https://doi.org/10.1245/s10434-022-12202-y

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