NRNAD+ precursor increases aerobic performance.

Fred

NAD+ precursor increases aerobic performance.

Post by Fred » Tue Sep 10, 2019 3:28 pm

In this mouse study the NAD precursor NR did not increase aerobic capacity on its own but combining NR supplementation and aerobic training increased the aerobic performance compared to the group that only trained (without NR).

PURPOSE:
Nicotinamide riboside (NR) acts as a potent NAD+ precursor and improves mitochondrial oxidative capacity and mitochondrial biogenesis in several organisms. However, the effects of NR supplementation on aerobic performance remain unclear.

Here, we evaluated the effects of NR supplementation on the muscle metabolism and aerobic capacity of sedentary and trained mice.

METHODS:
Male C57BL/6 J mice were supplemented with NR (400 mg/Kg/day) over 5 and 10 weeks. The training protocol consisted of 5 weeks of treadmill aerobic exercise, for 60 min a day, 5 days a week. Bioinformatic and physiological assays were combined with biochemical and molecular assays to evaluate the experimental groups.

RESULTS:
NR supplementation by itself did not change the aerobic performance, even though 5 weeks of NR supplementation increased NAD+ levels in the skeletal muscle.

However, combining NR supplementation and aerobic training increased the aerobic performance compared to the trained group. This was accompanied by an increased protein content of NMNAT3, the rate-limiting enzyme for NAD + biosynthesis and mitochondrial proteins, including MTCO1 and ATP5a.

Interestingly, the transcriptomic analysis using a large panel of isogenic strains of BXD mice confirmed that the Nmnat3 gene in the skeletal muscle is correlated with several mitochondrial markers and with different phenotypes related to physical exercise. Finally, NR supplementation during aerobic training markedly increased the amount of type I fibers in the skeletal muscle.

SUMMARY:
the improvement in exercise performance in trained and supplemented animals was accompanied by an increase in type I skeletal muscle fibers. The increase in oxidative fibers content is associated with better aerobic performance, since the type I fibers presented a larger number of myoglobin, which transports oxygen and a greater mitochondrial density [36].

Aerobic training can promote changes in fiber type, giving it an oxidative profile [1] and NR increases the mitochondrial content, which is the ideal combination to increase oxidative profile.

Moreover, combining NR and training may potentiate the action of SIRT1, since both strategies result in increased NAD + levels [6, 8]. SIRT1 induces PGC1-α deacetylation [8], which is associated with mitochondrial biogenesis in the skeletal muscle.

In summary, our intervention strategy, which involved combining NR and exercise training, increased NMNAT3 and mitochondrial proteins in the skeletal muscle, which are associated with better oxidative metabolism, results in an increase in exercise performance in mice, and thus suggests that NR supplementation could be an interesting ergogenic strategy to improve aerobic performance.

https://sci-hub.se/10.1007/s00394-019-02089-z


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nettlesbe
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Re: NAD+ precursor increases aerobic performance.

Post by nettlesbe » Sat Sep 14, 2019 1:58 pm

These were YOUNG mice, which is likely why NR by itself did not help.

Would really like to see if NR by itself increases endurance in older mice, like NMN does.

Another thing that stands out to me is, NR increased NAD+ levels in the muscle. In the recent study by Dr Brenner, NR did NOT increase NAD+ levels in human muscle. Why the different finding???

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Drdavid
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Re: NAD+ precursor increases aerobic performance.

Post by Drdavid » Sat Sep 14, 2019 4:19 pm

The research protocols for the two projects were different and therefore can lead to different results. You may have noticed that there were several positive results in this project that shows an increase in the NAD metabolome
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nettlesbe
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Re: NAD+ precursor increases aerobic performance.

Post by nettlesbe » Sat Sep 14, 2019 4:56 pm

Thanks, but I'm not sure what you are referring to.

They feed the mice 400mg/kg a day of NR for 5 weeks, which would be something like 2000 mg a day for a 70 kg human.

Dr Brenners study gave humans 1000 mg a day NR for 3 weeks.

Do you mean the different dosage, delivery method, or time length might explain why NAD+ levels were nearly doubled in mice, but no change to muscle NAD+ in humans?

I was thinking there might have been a difference in testing methodology.

A much less appealing explanation is that NR just works differently in humans vs mice.
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