Major surgery diminishes systemic arginine availability and suppresses nitric oxide response to feeding in patients with early stage breast cancer

Mariëlle P.K.J. Engelen, Vicki Klimberg, Arianna Allasia, Nicolaas E.P. Deutz

Research output: Contribution to journalArticle

Abstract

Background & aims: Plasma arginine (ARG) levels are reduced in breast cancer, suggesting diminished systemic ARG availability. ARG and its product nitric oxide (NO) are important in early postoperative recovery due to its roles in immune function and wound healing. It remains unclear whether major surgery further diminishes systemic ARG availability due to enhanced ARG catabolism and/or insufficient endogenous ARG synthesis negatively affecting NO synthesis in patients with early stage breast cancer. Methods: In 9 women with early stage breast malignancy and 9 healthy women with genetic predisposition to breast cancer, whole body ARG and citrulline (CIT) rates of appearances were measured to determine their production rates prior to and within 24 h after major breast surgery by stable isotope methodology in the postabsorptive and postprandial state. The conversions of CIT > ARG, ARG > CIT, and ARG > Urea (markers of de novo ARG and NO synthesis, arginase activity, respectively), and ARG clearance (reflecting ARG disposal capacity) were calculated. Results: Prior to surgery, plasma ARG, CIT and glutamine concentrations were lower in cancer (P < 0.05) but no differences were found in the rate of appearances of ARG, CIT and their conversions. Surgery increased ARG clearance and reduced CIT rate of appearance, conversion of CIT > ARG (P < 0.001), and plasma ARG, CIT, ornithine concentrations (P < 0.001). Furthermore, postprandial increase in ARG > CIT conversion (P < 0.05), plasma ARG (P < 0.001) and CIT (P = 0.06) concentrations were lower after surgery. The cancer group had lower values for postprandial increase in ARG > CIT conversion, plasma CIT (P < 0.05) and glutamine concentrations (P = 0.08). Conclusions: Major surgery in early stage breast cancer further reduces systemic ARG availability in the early phase of recovery due to a combined process of increased ARG catabolism and impaired endogenous ARG synthesis. The suppressed postprandial NO increase in early stage cancer suggests that specific nutritional approaches are advised to increase ARG availability after major surgery although the effects on postoperative recovery remain unclear.This trial was registered at clinicaltrials.gov as NCT00497380.

Original languageEnglish (US)
JournalClinical Nutrition
DOIs
StateAccepted/In press - 2017
Externally publishedYes

Fingerprint

Arginine
Nitric Oxide
Breast Neoplasms
Citrulline
Glutamine
Breast
Arginase
Neoplasms
Genetic Predisposition to Disease
Isotopes
Wound Healing
Urea

Keywords

  • Arginine kinetics
  • Breast surgery
  • Early stage breast cancer
  • Nitric oxide synthesis
  • Stable isotopes

ASJC Scopus subject areas

  • Nutrition and Dietetics
  • Critical Care and Intensive Care Medicine

Cite this

Major surgery diminishes systemic arginine availability and suppresses nitric oxide response to feeding in patients with early stage breast cancer. / Engelen, Mariëlle P.K.J.; Klimberg, Vicki; Allasia, Arianna; Deutz, Nicolaas E.P.

In: Clinical Nutrition, 2017.

Research output: Contribution to journalArticle

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title = "Major surgery diminishes systemic arginine availability and suppresses nitric oxide response to feeding in patients with early stage breast cancer",
abstract = "Background & aims: Plasma arginine (ARG) levels are reduced in breast cancer, suggesting diminished systemic ARG availability. ARG and its product nitric oxide (NO) are important in early postoperative recovery due to its roles in immune function and wound healing. It remains unclear whether major surgery further diminishes systemic ARG availability due to enhanced ARG catabolism and/or insufficient endogenous ARG synthesis negatively affecting NO synthesis in patients with early stage breast cancer. Methods: In 9 women with early stage breast malignancy and 9 healthy women with genetic predisposition to breast cancer, whole body ARG and citrulline (CIT) rates of appearances were measured to determine their production rates prior to and within 24 h after major breast surgery by stable isotope methodology in the postabsorptive and postprandial state. The conversions of CIT > ARG, ARG > CIT, and ARG > Urea (markers of de novo ARG and NO synthesis, arginase activity, respectively), and ARG clearance (reflecting ARG disposal capacity) were calculated. Results: Prior to surgery, plasma ARG, CIT and glutamine concentrations were lower in cancer (P < 0.05) but no differences were found in the rate of appearances of ARG, CIT and their conversions. Surgery increased ARG clearance and reduced CIT rate of appearance, conversion of CIT > ARG (P < 0.001), and plasma ARG, CIT, ornithine concentrations (P < 0.001). Furthermore, postprandial increase in ARG > CIT conversion (P < 0.05), plasma ARG (P < 0.001) and CIT (P = 0.06) concentrations were lower after surgery. The cancer group had lower values for postprandial increase in ARG > CIT conversion, plasma CIT (P < 0.05) and glutamine concentrations (P = 0.08). Conclusions: Major surgery in early stage breast cancer further reduces systemic ARG availability in the early phase of recovery due to a combined process of increased ARG catabolism and impaired endogenous ARG synthesis. The suppressed postprandial NO increase in early stage cancer suggests that specific nutritional approaches are advised to increase ARG availability after major surgery although the effects on postoperative recovery remain unclear.This trial was registered at clinicaltrials.gov as NCT00497380.",
keywords = "Arginine kinetics, Breast surgery, Early stage breast cancer, Nitric oxide synthesis, Stable isotopes",
author = "Engelen, {Mari{\"e}lle P.K.J.} and Vicki Klimberg and Arianna Allasia and Deutz, {Nicolaas E.P.}",
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T1 - Major surgery diminishes systemic arginine availability and suppresses nitric oxide response to feeding in patients with early stage breast cancer

AU - Engelen, Mariëlle P.K.J.

AU - Klimberg, Vicki

AU - Allasia, Arianna

AU - Deutz, Nicolaas E.P.

PY - 2017

Y1 - 2017

N2 - Background & aims: Plasma arginine (ARG) levels are reduced in breast cancer, suggesting diminished systemic ARG availability. ARG and its product nitric oxide (NO) are important in early postoperative recovery due to its roles in immune function and wound healing. It remains unclear whether major surgery further diminishes systemic ARG availability due to enhanced ARG catabolism and/or insufficient endogenous ARG synthesis negatively affecting NO synthesis in patients with early stage breast cancer. Methods: In 9 women with early stage breast malignancy and 9 healthy women with genetic predisposition to breast cancer, whole body ARG and citrulline (CIT) rates of appearances were measured to determine their production rates prior to and within 24 h after major breast surgery by stable isotope methodology in the postabsorptive and postprandial state. The conversions of CIT > ARG, ARG > CIT, and ARG > Urea (markers of de novo ARG and NO synthesis, arginase activity, respectively), and ARG clearance (reflecting ARG disposal capacity) were calculated. Results: Prior to surgery, plasma ARG, CIT and glutamine concentrations were lower in cancer (P < 0.05) but no differences were found in the rate of appearances of ARG, CIT and their conversions. Surgery increased ARG clearance and reduced CIT rate of appearance, conversion of CIT > ARG (P < 0.001), and plasma ARG, CIT, ornithine concentrations (P < 0.001). Furthermore, postprandial increase in ARG > CIT conversion (P < 0.05), plasma ARG (P < 0.001) and CIT (P = 0.06) concentrations were lower after surgery. The cancer group had lower values for postprandial increase in ARG > CIT conversion, plasma CIT (P < 0.05) and glutamine concentrations (P = 0.08). Conclusions: Major surgery in early stage breast cancer further reduces systemic ARG availability in the early phase of recovery due to a combined process of increased ARG catabolism and impaired endogenous ARG synthesis. The suppressed postprandial NO increase in early stage cancer suggests that specific nutritional approaches are advised to increase ARG availability after major surgery although the effects on postoperative recovery remain unclear.This trial was registered at clinicaltrials.gov as NCT00497380.

AB - Background & aims: Plasma arginine (ARG) levels are reduced in breast cancer, suggesting diminished systemic ARG availability. ARG and its product nitric oxide (NO) are important in early postoperative recovery due to its roles in immune function and wound healing. It remains unclear whether major surgery further diminishes systemic ARG availability due to enhanced ARG catabolism and/or insufficient endogenous ARG synthesis negatively affecting NO synthesis in patients with early stage breast cancer. Methods: In 9 women with early stage breast malignancy and 9 healthy women with genetic predisposition to breast cancer, whole body ARG and citrulline (CIT) rates of appearances were measured to determine their production rates prior to and within 24 h after major breast surgery by stable isotope methodology in the postabsorptive and postprandial state. The conversions of CIT > ARG, ARG > CIT, and ARG > Urea (markers of de novo ARG and NO synthesis, arginase activity, respectively), and ARG clearance (reflecting ARG disposal capacity) were calculated. Results: Prior to surgery, plasma ARG, CIT and glutamine concentrations were lower in cancer (P < 0.05) but no differences were found in the rate of appearances of ARG, CIT and their conversions. Surgery increased ARG clearance and reduced CIT rate of appearance, conversion of CIT > ARG (P < 0.001), and plasma ARG, CIT, ornithine concentrations (P < 0.001). Furthermore, postprandial increase in ARG > CIT conversion (P < 0.05), plasma ARG (P < 0.001) and CIT (P = 0.06) concentrations were lower after surgery. The cancer group had lower values for postprandial increase in ARG > CIT conversion, plasma CIT (P < 0.05) and glutamine concentrations (P = 0.08). Conclusions: Major surgery in early stage breast cancer further reduces systemic ARG availability in the early phase of recovery due to a combined process of increased ARG catabolism and impaired endogenous ARG synthesis. The suppressed postprandial NO increase in early stage cancer suggests that specific nutritional approaches are advised to increase ARG availability after major surgery although the effects on postoperative recovery remain unclear.This trial was registered at clinicaltrials.gov as NCT00497380.

KW - Arginine kinetics

KW - Breast surgery

KW - Early stage breast cancer

KW - Nitric oxide synthesis

KW - Stable isotopes

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