Why does Dr. Sinclair choose NMN over NR?

There has been little, if any, direct comparison studies between Nicotinamide Mononucleotide (NMN) and Nicotinamide Riboside (NMR) (NR).However, Dr. Sinclair recently said he takes NMN instead of NR based on research he did that found NR did not work at all, while NMN increased the endurance in older mice such that they were able to run twice as far as those on placebo.Why choose NMN?

“NMN makes mice run further. Old mice can run 50% further, because they have better blood flow, better energy. NR at the same dose did not do that. In fact it had NO EFFECT.” (Dr. David Sinclair)


He is referencing this research, but unfortunately, they did not publish the results they found with NR.  See our review here.

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Why does Dr. Sinclair choose NMN over NR?

NMN has much stronger record of benefit to humans in clinical studies

Several human clinical trials with NR have been published in recent years, whereas those with NMN have lagged behind, leading some to believe that NR is the “safer” bet.

That story was turned on its head in 2022, when three clinical studies using NMN were released. One was a safety trial only (r). The other 2 were successful in showing some benefit to humans (r,r).

Despite the fact that more than 11 clinical trials with NR have now been published, practically all of them have failed to show any benefit in humans. The only apparent exception is this 2022 study that shows a decrease in the inflammatory marker IL-6. We’ll go over that later.

The use of NMN improved muscle insulin sensitivity

In this trial, the muscle insulin sensitivity was assessed as the rate of insulin-stimulated glucose disposal per kg of fat-free mass during the clamp procedure. In plain words, they measured how quickly and efficiently the glucose is taken up from blood in response to the insulin.A higher insulin-stimulated glucose disposal rate indicates greater insulin sensitivity, which is associated with improved metabolic health.

The insulin-stimulated glucose disposal rate increased by 27% in the participants after 10 weeks of NMN administration, but not placebo. This increase in muscle insulin sensitivity is clinically significant and comparable to the improvement seen following a 10% weight loss (equivalent to roughly 20 pounds weight loss in the subjects). This finding implies that increasing NAD+ turnover rather than modifying muscle NAD+ concentration enhanced insulin sensitivity and maybe metabolic health.

See Alive By Science full review here

In clinical trials, NR did not enhance insulin sensitivity

Several randomized controlled trials in middle-aged and older-adult men demonstrated that treatment with nicotinamide riboside (NR) had no effect on whole-body or muscle insulin sensitivity, in contrast to the insulin-sensitizing effects of NMN.

Even though, compared with the administration of 250 mg NMN in this trial, these NR trials used a higher dose of NR with a similar time: 2000 mg for 12 weeks in Dollerup et al. (2018); 1000 mg for 3 and 6 weeks in Elhassan et al. (2019) and Remie et al. (2020).

“Insulin sensitivity, endogenous glucose production, and glucose disposal and oxidation were not improved by NR supplementation.” (r)

“There were no changes in body weight, blood pressure, lipid profile, fasting glucose and insulin (Table S1), and homeostatic model assessment of insulin resistance…NR did not produce this effect in our trial “(r)

“However, insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma indicators of inflammation, or energy metabolism were not shown to be affected by NR.”(r)

This could mean that NMN delivers more metabolic benefits than NR because it is the rate-limiting element in NAD+ production. However, due to the complexities of demographic variability and sample size limitations, more research is needed to answer this topic.

Why choose NMN

NMN enhances aerobic capacity in amateur runners: a randomized, double-blind study

In this six-week human study published July 8, 2022,the researchers concluded that supplementing amateur runners with Nicotinamide Mononucleotide (NMN) significantly increased their ventilatory threshold (VT). It was a dose-dependent and muscle-related advantage.

The Guangzhou Pearl River running team conducted a randomized, double-blind, placebo-controlled, four-arm clinical trial to explore the effects of a combination of exercise training and NMN supplementation on 48 young and middle-aged recreationally trained runners.

  • Even healthy young athletes have a higher ventilatory threshold.
  • The increased O2 utilization of the skeletal muscle is most likely the cause of the greater aerobic capacity.
  • The improvement is muscle-related rather than cardiac-related.
  • The rate at which aerobic capacity improves is dose-dependent.
  • Larger NMN doses produce better effects.
  • After 6 weeks of dosage, the following results were obtained.

See the alivebyscience full review here

NR does show possible benefit for decreased inflammation in skeletal muscle

The Dollerup et al  study mentioned above did not find any benefit for insulin sensitiviy that was a primary objective, but did find a significant decrease in the IL-6 marker for inflammation.

Although the sample size was insufficient to detect NR-driven changes in the NAD+ metabolome, muscle transcriptional signature, and inflammatory profile, the trial’s sample size was sufficient to detect NR-driven changes in the NAD+ metabolome, muscle transcriptional signature, and inflammatory profile. The transcriptional downregulation of mitochondrial gene sets further refutes the possibility that the lack of a bioenergetic NR effect is due to sample size limitations. More research is needed to fully understand some of the NR-mediated alterations observed in this experimental medicine investigation.

Overall, these investigations show that oral NR can reach human skeletal muscle and that it has anti-inflammatory characteristics, both of which could be useful in the context of aging, muscle disease, or inflammatory disease.

Why choose NMN

Conclusion

Humans gain more from NMN than NR, according to published data. Of course, we’re still in the early stages of study, and we’ll need to do a lot more to figure out which NAD+ boosting substances are best for certain tissues or disorders.

Dr. Sinclair may favor NMN to NR, but he has been predicting that different NAD+ precursors will be proved to benefit different tissues since at least 2016.

Alive By Science agree that there is not one “best” NAD+ precursor, but that they are able to reach different tissues.  That is why Alive By Science sell NAD+, NMN, and NR supplements.

We also believe that other strategies such as lowering inflammation and decreasing CD38 to minimize NAD+ consumption will be proven to be beneficial to humans.

Why choose NMN

Why choose NMN

Alive by Science review – Do these NMN supplements fight aging?

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