Carnitine supplementation improves metabolic flexibility and skeletal muscle acetylcarnitine formation in volunteers with impaired glucose tolerance: A randomised controlled trial

Yvonne Mh Bruls, Marlies de Ligt, Lucas Lindeboom, Esther Phielix, Bas Havekes, Gert Schaart, Esther Kornips, Joachim E Wildberger, Matthijs Kc Hesselink, Deborah Muoio, Patrick Schrauwen, Vera B Schrauwen-Hinderling

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: Type 2 diabetes patients and individuals at risk of developing diabetes are characterized by metabolic inflexibility and disturbed glucose homeostasis. Low carnitine availability may contribute to metabolic inflexibility and impaired glucose tolerance. Here, we investigated whether carnitine supplementation improves metabolic flexibility and insulin sensitivity in impaired glucose tolerant (IGT) volunteers.

METHODS: Eleven IGT- volunteers followed a 36-day placebo- and L-carnitine treatment (2 g/day) in a randomised, placebo-controlled, double blind crossover design. A hyperinsulinemic-euglycemic clamp (40 mU/m2/min), combined with indirect calorimetry (ventilated hood) was performed to determine insulin sensitivity and metabolic flexibility. Furthermore, metabolic flexibility was assessed in response to a high-energy meal. Skeletal muscle acetylcarnitine concentrations were measured in vivo using long echo time proton magnetic resonance spectroscopy (1H-MRS, TE=500 ms) in the resting state (7:00AM and 5:00PM) and after a 30-min cycling exercise. Twelve normal glucose tolerant (NGT) volunteers were included without any intervention as control group.

RESULTS: Metabolic flexibility of IGT-subjects completely restored towards NGT control values upon carnitine supplementation, measured during a hyperinsulinemic-euglycemic clamp and meal test. In muscle, carnitine supplementation enhanced the increase in resting acetylcarnitine concentrations over the day (delta 7:00 AM versus 5:00 PM) in IGT-subjects. Furthermore, carnitine supplementation increased post-exercise acetylcarnitine concentrations and reduced long-chain acylcarnitine species in IGT-subjects, suggesting the stimulation of a more complete fat oxidation in muscle. Whole-body insulin sensitivity was not affected.

CONCLUSION: Carnitine supplementation improves acetylcarnitine formation and rescues metabolic flexibility in IGT-subjects. Future research should investigate the potential of carnitine in prevention/treatment of type 2 diabetes.

Original languageEnglish
Pages (from-to)318-330
Number of pages13
JournalEBioMedicine
Volume49
DOIs
Publication statusPublished - Nov 2019
Externally publishedYes

Keywords

  • acetylcarnitine/blood
  • body composition/drug effects
  • carnitine/blood
  • dietary supplements
  • female
  • glucose tolerance test
  • glycogen/metabolism
  • healthy volunteers
  • humans
  • hyperinsulinism/blood
  • insulin resistance
  • kinetics
  • male
  • metabolome
  • middle aged
  • muscle, skeletal/metabolism
  • oxygen consumption/drug effects

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