NMNThe first NMN study in humans is published

Fred
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Re: The first NMN study in humans is published

Post by Fred » Fri Nov 08, 2019 12:49 pm

We only have published human NAD-boosting results with NR, nicotinic acid (NA) and nicotinamide (NAM) at the moment. All three can increase NAD in various tissues to a different extent, but NAM exhibits negative feedback inhibition on NAD-synthesis and in high doses inhibits sirtuins. Coming human trials will show how NMN compares to the others so we don´t have to speculate.


Fred
Registered dietitian, Sweden.
canadahealthy
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Re: The first NMN study in humans is published

Post by canadahealthy » Fri Nov 08, 2019 3:09 pm

Fred wrote:
Fri Nov 08, 2019 12:49 pm
We only have published human NAD-boosting results with NR, nicotinic acid (NA) and nicotinamide (NAM) at the moment. All three can increase NAD in various tissues to a different extent, but NAM exhibits negative feedback inhibition on NAD-synthesis and in high doses inhibits sirtuins. Coming human trials will show how NMN compares to the others so we don´t have to speculate.
Perfect! Now everyone leave Fred alone!
Fred
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Re: The first NMN study in humans is published

Post by Fred » Fri Nov 08, 2019 3:47 pm

It´s fun to speculate of course. But it will be nice to get some human pharmacokinetic data on NMN in the near future, so we don´t need to guess or hope.
Fred
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ALIVEBYNATURE
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Re: The first NMN study in humans is published

Post by ALIVEBYNATURE » Sun Nov 17, 2019 3:04 pm

It is quite unfortunate they didn't measure NAD+.

They say MeNAM 2py and 4py are end products of NAD+ degradation, so increase in those metabolites indicate increase in NAD+.

Dr Brenner said the same thing on the GRAS application for NR:
The pharmacokinetic analysis from the first in human clinical study (14NBHC) shows that Methyl-nicotinamide (MeN am), Py 4 and Py 2 are predominant NAD+ related metabolites that appear within hours after ingestion of a single dose of Niagen.

Methyl-nicotinamide is a biomarker of niacin status and correlates with NAD+ levels in red blood cells in humans. (Jacob et al., 1989; Fu et al., 1989). Moreover MeNam, Py 4 and Py 2 concentrations in urine correlate with the levels of niacin intake and NAD+ levels in humans. (Jacob et al., 1989; Fu et al., 1989; Shibata et al., 1989).

One thing that does seem clear, is that NMN was converted to 2py and 4py much faster than when taking NR. 1 hour, vs 3-4 hours. charts below.

I wrote a short post about this here:

https://alivebynature.com/1st-nmn-human ... n-than-nr/



Image

Image
Fred
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Re: The first NMN study in humans is published

Post by Fred » Sun Nov 17, 2019 3:37 pm

Nice breakdown of the study in the blog post ^^
Fred
Registered dietitian, Sweden.
vandan
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Re: The first NMN study in humans is published

Post by vandan » Sun Nov 17, 2019 5:49 pm

Fred wrote:
Thu Nov 07, 2019 11:57 pm
The single oral administration of NMN capsules in the doses
100, 250 and 500 mg in 10 healthy Japanese men was shown to be safe.

"Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men"

The administration of nicotinamide mononucleotide (NMN) has been shown to mitigate aging-related dysfunctions. However, the safety of NMN in humans have remained unclear.

We, therefore, conducted a clinical trial to investigate the safety of single NMN administration in 10 healthy men. A single-arm non-randomized intervention was conducted by single oral administration of 100, 250, and 500 mg NMN.

Clinical findings and parameters, and the pharmacokinetics of NMN metabolites were investigated for 5 h after each intervention. Ophthalmic examination and sleep quality assessment were also conducted before and after the intervention.

The single oral administrations of NMN did not cause any significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation, and body temperature.

Laboratory analysis results did not show significant changes, except for increases in serum bilirubin levels and decreases in serum creatinine, chloride, and blood glucose levels within the normal ranges, independent of the dose of NMN.

Results of ophthalmic examination and sleep quality score showed no differences before and after the intervention. Plasma concentrations of N-methyl-2-pyridone-5- carboxamide and N-methyl-4-pyridone-5-carboxamide were significantly increased dose-dependently by NMN administration.

The single oral administration of NMN was safe and effectively metabolized in healthy men without causing any significant deleterious effects. Thus, the oral administration of NMN was found to be feasible, implicating a potential therapeutic strategy to mitigate aging-related disorders in humans.

https://www.jstage.jst.go.jp/article/en ... f/-char/en
If this is the first study then the opening statement cannot be responsibly made. I look forward to more rigorous trials.
vandan
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Re: The first NMN study in humans is published

Post by vandan » Sun Nov 17, 2019 5:56 pm

vandan wrote:
Sun Nov 17, 2019 5:49 pm
Fred wrote:
Thu Nov 07, 2019 11:57 pm
The single oral administration of NMN capsules in the doses
100, 250 and 500 mg in 10 healthy Japanese men was shown to be safe.

oh, your cut and past missed the first and important sentence....

Recent studies have revealed that decline in cellular nicotinamide adenine dinucleotide (NAD+) levels causes aging-related disorders and therapeutic approaches increasing cellular NAD+ prevent these disorders in animal models.

Lesson 101 again! always check the source data.

"Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men"

The administration of nicotinamide mononucleotide (NMN) has been shown to mitigate aging-related dysfunctions. However, the safety of NMN in humans have remained unclear.

We, therefore, conducted a clinical trial to investigate the safety of single NMN administration in 10 healthy men. A single-arm non-randomized intervention was conducted by single oral administration of 100, 250, and 500 mg NMN.

Clinical findings and parameters, and the pharmacokinetics of NMN metabolites were investigated for 5 h after each intervention. Ophthalmic examination and sleep quality assessment were also conducted before and after the intervention.

The single oral administrations of NMN did not cause any significant clinical symptoms or changes in heart rate, blood pressure, oxygen saturation, and body temperature.

Laboratory analysis results did not show significant changes, except for increases in serum bilirubin levels and decreases in serum creatinine, chloride, and blood glucose levels within the normal ranges, independent of the dose of NMN.

Results of ophthalmic examination and sleep quality score showed no differences before and after the intervention. Plasma concentrations of N-methyl-2-pyridone-5- carboxamide and N-methyl-4-pyridone-5-carboxamide were significantly increased dose-dependently by NMN administration.

The single oral administration of NMN was safe and effectively metabolized in healthy men without causing any significant deleterious effects. Thus, the oral administration of NMN was found to be feasible, implicating a potential therapeutic strategy to mitigate aging-related disorders in humans.

https://www.jstage.jst.go.jp/article/en ... f/-char/en
If this is the first study then the opening statement cannot be responsibly made. I look forward to more rigorous trials.
Drdavid
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Re: The first NMN study in humans is published

Post by Drdavid » Sun Nov 17, 2019 7:32 pm

We must remember that we are on a frontier in longevity medicine. The current research is limited but does seem to be promising in many areas. Most notably is the neurodegenerative field and stroke field but even these studies provide limited data on a limited subject sample. The real data is yet to come in the form of a large scale study and this is where we start to understand the true pharmacologic implications in humans. For now we have to speculate in the clinical world and use the data that we have from patients. We will see changes in dosing and protocol as the data becomes more clear but for now work a regimen that provides you with the best results.
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