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
Affiliations
Yvonne MH Bruls
Department of Radiology and Nuclear Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands; Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands
Marlies de Ligt
Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands
Lucas Lindeboom
Department of Radiology and Nuclear Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands; Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands
Esther Phielix
Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands
Bas Havekes
Department of Internal Medicine, Division of Endocrinology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands
Gert Schaart
Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands
Esther Kornips
Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands
Joachim E Wildberger
Department of Radiology and Nuclear Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands
Matthijs KC Hesselink
Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands
Deborah Muoio
Department of Medicine, Duke University Medical Center, Durham, NC NC22704, United States of America
Patrick Schrauwen
Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands
Vera B Schrauwen-Hinderling
Department of Radiology and Nuclear Medicine, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands; Department of Nutrition and Movement Sciences, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6200 MD Maastricht, the Netherlands; Corresponding author at: Department of Radiology and Nuclear Medicine, Department of Nutrition and Movement Sciences, Maastricht University Medical Center, P.O. BOX 616, 6200 MD Maastricht, the Netherlands.
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. Keywords: L-carnitine, Metabolic flexibility, Insulin sensitivity, Acetylcarnitine, Impaired glucose tolerance, Hyperinsulinemic-euglycemic clamp
