NOT A PEER REVIEWED PAPER
Fat mice on a treadmill treated with NMN did worse than control with regard to glucose handling.
The authors conclude:
"Our data suggest that NMN administration at 400mg/kg in drinking water could drive an antioxidative response which may have mitigated the transient increase in ROS after exercise, which is crucial for exercise-induced health benefits such as improved insulin secretion in response to glucose stimulation and metabolic adaptation. "
and
"These results argue against the idea that combining NMN-supplementation and exercise would have additive benefits in the treatment of obesity, and warrant caution in the use of NAD+ precursors in situations where NAD+ is already replete."
So when are NAD-levels replete? At 500 mg, 750 mg or 1000 mg of NMN? Even higher in some disease states? We still have lot to learn about dose-response and benefits-harm when it comes to NAD+ precursors.
The mice were treated with 400 mg of NMN/kg in drinking water. That equals 32 mg/kg of NMN in a human. That is 2240 mg of NMN for a 70 kg human.
ABSTRACT
Highlights
-
NMN dampened exercise-induced benefits on glucose handling in diet-induced obesity.
-
NMN administration in exercise enhanced ratio of antioxidants to prooxidants.
-
We suggest NMN administration may not be beneficial when NAD+ levels are replete.
Objective Almost 40% of adults worldwide are classified as overweight or obese. Exercise is a beneficial intervention in obesity, partly due to increases in mitochondrial activity, with a potential role for the concomitant increase in nicotinamide adenine dinucleotide (NAD+). Recent studies have shown that increasing NAD+ levels through pharmacological supplementation with precursors such as nicotinamide mononucleotide (NMN) improved metabolic health in high fat diet (HFD) fed mice. We examined the combined effects of NMN and treadmill exercise on the metabolic dysregulation in HFD-induced obesity.
Methods Five-week old female C57BL/6J mice were exposed to control diet or HFD. Mice fed HFD were treated with NMN in drinking water (400mg/kg; HNMN), treadmill exercise (HEx) or combined NMN and exercise (HNEx).
Results Unexpectedly, NMN administration impaired several aspects of exercise-induced benefits in HFD mice, including glucose tolerance, glucose stimulated insulin secretion from islets and reduced hepatic triglyceride accumulation. Mechanistically, HNEx mice displayed increased antioxidant and reduced prooxidant gene expression in both islets and muscle, suggesting that altered redox status is associated with the loss of exercise-induced health benefits with NMN co-treatment.
Conclusion Our data show that NMN treatment blocks the beneficial metabolic effects of exercise in a mouse model of diet-induced obesity in association with disturbances in redox metabolism.
https://www.biorxiv....2.164459v1.full
Edited by Linux, 16 July 2020 - 07:42 AM.