Metabolic phenotyping to provide insight in mechanisms underlying muscle weakness and wasting in patients with cancer

Barbara S Van der Meij, Nicolaas Deutz, Ramon Rodriguez, Fari Koeman, Tiffany Smit, Marielle Engelen

Research output: Contribution to journalMeeting AbstractResearchpeer-review

Abstract

Rationale: Cancer is characterized by low plasma concentrations of arginine (ARG), glutamine (GLN) and citrulline (CIT). This study investigates the relationship between glutamine-related metabolism and muscle strength in patients with advanced cancer using metabolic phenotyping.
Methods: In 16 patients with solid tumours (C) and 16 age- and gender-matched healthy controls (H), fasted plasma amino acid concentrations and whole body ARG, GLN, CIT and GLU rates of appearance (Ra) were assessed by pulse IV administration of L-[Guanidino-15N2]-Arginine, L-[5-15N]-glutamine, L-[ureido-13C-2H2]-Citrulline, L-[1,2-13C2] Glutamate and 2H3-Leucine (LEU), and clearance rates calculated. Handgrip, inspiratory and leg muscle strength and physical function (EORTC-QLQc30 questionnaire) were assessed, and amino acid concentrations and isotope enrichments by LCMS/MS. Statistics was done by unpaired t-tests and spearman correlation tests.
Results: Ra and clearance rate of GLN were higher in C than in H (Ra GLN: 491.4±32.0 vs. 325.2±51.5 μmol/kg ffm/h, p=0.008, clearance GLN 1.13±0.08 vs 0.70±0.09, p<0.001) as well as that of the GLN related amino acids ARG, CIT and LEU (p<0.05). The conversion of ARG to CIT (marker of NO synthesis), CIT to ARG (de novo ARG production) and GLU to GLN (marker of muscle GLN production) were also higher in C (P<0.01) and negatively correlated to FFMi (r<-0.5, P<0.05). Plasma BCAA was positively correlated to handgrip and inspiratory muscle strength, and physical function (R>0.4, P<0.05). RaCIT was negatively related to leg extension strength (r=-0.7, P<0.01).
Conclusion: Metabolic phenotyping using novel tracer pulse methodology showed that disturbances in glutamine related metabolism are associated with muscle wasting and weakness in patients with cancer.
Original languageEnglish
Pages (from-to)S156
JournalClinical Nutrition
Volume36
Issue numberS1
DOIs
Publication statusPublished - Sep 2017
EventThe 39th European Society for Clinical Nutrition and Metabolism Congress 2017 - Hague, Netherlands
Duration: 9 Sep 201712 Sep 2017
Conference number: 39
http://www.espen.org/congress/next-congresses/12-espen/index.php?option=com_content&view=article&id=214&Itemid=1052

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    • 2 Meeting Abstract

    Depressed mood and cognitive functions in patients with cancer are associated with alterations in tryptophan metabolism

    Van der Meij, B. S., Lieben, C. K., Deutz, N. E. P., Rodriguez, R. E., Koeman, F., Smit, T. & Engelen, M., Sep 2017, In : Clinical Nutrition. 36, S1, p. S70 1 p.

    Research output: Contribution to journalMeeting AbstractResearchpeer-review

    Open Access
  • Increased amino acid turnover and myofibrillar protein breakdown in advanced cancer are associated with decreased muscle strength and physical function

    Van der Meij, B. S., Deutz, N., Rodriguez, R., Koeman, F., Smit, T. & Engelen, M., Sep 2017, In : Clinical Nutrition. 36, Supplement 1, p. S46-S47 2 p.

    Research output: Contribution to journalMeeting AbstractResearchpeer-review

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