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Poor Results from an Initial Human Trial of Nicotinamide Mononucleotide


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#1 reason

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Posted 11 November 2019 - 09:06 PM


Mitochondria are the power plants of the cell, responsible for packaging energy store molecules that power cellular processes. NAD+ is an essential metabolite for mitochondrial function, but levels decline with age. The proximate causes of this decline are fairly well mapped, and involve insufficient resources in a variety of pathways for synthesis or recycling of NAD+. The deeper reasons are poorly understood, however, meaning how these pathway issues emerge from the underlying molecular damage to cells and tissues that causes aging. Ways to force an increase in NAD+ levels have been shown to improve mitochondrial function in old animals, reversing some of the losses that occur with age. Loss of mitochondrial function is implicated in age-related diseases, particularly those in energy-hungry tissues such as the brain and muscles.

There are a number of ways to raise NAD+ levels: delivery of sizable amounts of NAD+ directly via infusion, of which a tiny fraction makes it into cells where it is needed; delivery of various precursor molecules that are used to manufacture NAD+; or delivery of factors known to improve recycling of NAD+. Most present effort is focused on the second of those options, via supplements such as nicotinamide riboside or nicotinamide mononucleotide, though groups like Nuchido are trying to produce better means of raising NAD+ levels that target multiple mechanisms at once.

Nicotinamide riboside has been trialed in humans, in a small number of people, with data showing reductions in age-related increases in blood pressure through improvement in the function of vascular smooth muscle. A similarly small trial of nicotinamide mononucleotide took place in Japan, and in today's open access paper, the researchers involved report on the results. As you can see from their summary, this approach achieved none of the benefits noted in the trial of nicotinamide riboside. At least some of the patients were old enough to expect some positive outcome on blood pressure, but none was observed.

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. 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 of 40 to 60 years of age.

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 hours 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.

Link: https://doi.org/10.1...docrj.EJ19-0313


View the full article at FightAging

#2 Kentavr

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Posted 12 November 2019 - 04:03 PM

Conclusion: if you want to lower the pressure, use other drugs. :)

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