TY - JOUR
T1 - Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans
AU - Remie, Carlijn M. E.
AU - Roumans, Kay H. M.
AU - Moonen, Michiel P. B.
AU - Connell, Niels J.
AU - Havekes, Bas
AU - Mevenkamp, Julian
AU - Lindeboom, Lucas
AU - de Wit, Vera H. W.
AU - van de Weijer, Tineke
AU - Aarts, Suzanne A. B. M.
AU - Lutgens, Esther
AU - Schomakers, Bauke V.
AU - Elfrink, Hyung L.
AU - Zapata-Perez, Ruben
AU - Houtkooper, Riekelt H.
AU - Auwerx, Johan
AU - Hoeks, Joris
AU - Schrauwen-Hinderling, Vera B.
AU - Phielix, Esther
AU - Schrauwen, Patrick
PY - 2020/8
Y1 - 2020/8
N2 - Background: Nicotinamide riboside (NR) is an NAD(+) precursor that boosts cellular NAD(+) concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation.Objectives: We aimed to investigate the effects of 6 wk NR supplementation on insulin sensitivity, mitochondrial function, and other metabolic health parameters in overweight and obese volunteers.Methods: A randomized, double-blinded, placebo-controlled, crossover intervention study was conducted in 13 healthy overweight or obese men and women. Participants received 6 wk NR (1000 mg/d) and placebo supplementation, followed by broad metabolic phenotyping, including hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy, muscle biopsies, and assessment of ex vivo mitochondrial function and in vivo energy metabolism.Results: Markers of increased NAD(+) synthesis-nicotinic acid adenine dinucleotide and methyl nicotinamide-were elevated in skeletal muscle after NR compared with placebo. NR increased body fat-free mass (62.65% +/- 2.49% compared with 61.32% +/- 2.58% in NR and placebo, respectively; change: 1.34% +/- 0.50%, P = 0.02) and increased sleeping metabolic rate. Interestingly, acetylcarnitine concentrations in skeletal muscle were increased upon NR (4558 +/- 749 compared with 3025 +/- 316 pmol/mg dry weight in NR and placebo, respectively; change: 1533 +/- 683 pmol/mg dry weight, P = 0.04) and the capacity to form acetylcarnitine upon exercise was higher in NR than in placebo (2.99 +/- 0.30 compared with 2.40 +/- 0.33 mmol/kg wet weight; change: 0.53 +/- 0.21 mmol/kg wet weight, P = 0.01). However, no effects of NR were found on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism.Conclusions: NR supplementation of 1000 mg/d for 6 wk in healthy overweight or obese men and women increased skeletal muscle NAD(+) metabolites, affected skeletal muscle acetylcarnitine metabolism, and induced minor changes in body composition and sleeping metabolic rate. However, no other metabolic health effects were observed.
AB - Background: Nicotinamide riboside (NR) is an NAD(+) precursor that boosts cellular NAD(+) concentrations. Preclinical studies have shown profound metabolic health effects after NR supplementation.Objectives: We aimed to investigate the effects of 6 wk NR supplementation on insulin sensitivity, mitochondrial function, and other metabolic health parameters in overweight and obese volunteers.Methods: A randomized, double-blinded, placebo-controlled, crossover intervention study was conducted in 13 healthy overweight or obese men and women. Participants received 6 wk NR (1000 mg/d) and placebo supplementation, followed by broad metabolic phenotyping, including hyperinsulinemic-euglycemic clamps, magnetic resonance spectroscopy, muscle biopsies, and assessment of ex vivo mitochondrial function and in vivo energy metabolism.Results: Markers of increased NAD(+) synthesis-nicotinic acid adenine dinucleotide and methyl nicotinamide-were elevated in skeletal muscle after NR compared with placebo. NR increased body fat-free mass (62.65% +/- 2.49% compared with 61.32% +/- 2.58% in NR and placebo, respectively; change: 1.34% +/- 0.50%, P = 0.02) and increased sleeping metabolic rate. Interestingly, acetylcarnitine concentrations in skeletal muscle were increased upon NR (4558 +/- 749 compared with 3025 +/- 316 pmol/mg dry weight in NR and placebo, respectively; change: 1533 +/- 683 pmol/mg dry weight, P = 0.04) and the capacity to form acetylcarnitine upon exercise was higher in NR than in placebo (2.99 +/- 0.30 compared with 2.40 +/- 0.33 mmol/kg wet weight; change: 0.53 +/- 0.21 mmol/kg wet weight, P = 0.01). However, no effects of NR were found on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism.Conclusions: NR supplementation of 1000 mg/d for 6 wk in healthy overweight or obese men and women increased skeletal muscle NAD(+) metabolites, affected skeletal muscle acetylcarnitine metabolism, and induced minor changes in body composition and sleeping metabolic rate. However, no other metabolic health effects were observed.
KW - nicotinamide riboside
KW - NAD
KW - metabolic health
KW - insulin sensitivity
KW - mitochondrial function
KW - acetylcarnitine
KW - body composition
KW - human
KW - obesity
KW - AMBULATORY BLOOD-PRESSURE
KW - NAD(+)
KW - METABOLISM
KW - INSULIN
KW - DIET
KW - SPECTROSCOPY
KW - RESVERATROL
KW - RISK
U2 - 10.1093/ajcn/nqaa072
DO - 10.1093/ajcn/nqaa072
M3 - Article
C2 - 32320006
VL - 112
SP - 413
EP - 426
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
SN - 0002-9165
IS - 2
ER -