A formulation that maximizes the efficacy of NMN

Efficacy and effects of NMN and pterostilbene taken together

[ Getting to the point first ]

• Why should you take NMN and resveratrol together, as mentioned in 'The End of Aging'?
  
  NMN (nicotinamide mononucleotide) is converted to NAD+ within cells and used as fuel for the longevity gene, sirtuin. Resveratrol, on the other hand, acts as an activator of the longevity gene, sirtuin. Therefore, when taken together, the two substances have a synergistic anti-aging effect.

• Which ingredient, resveratrol or pterostilbene, will synergize with NMN?
  
  

  NMN and pterostilbene are an optimal combination for anti-aging, and when taken together, they help delay aging because NAD+ stays in our bodies much longer.
  
  When resveratrol is subjected to the action of O-Methyltransferase, the two hydroxyl hydrogens are replaced with methyl groups, converting it to pterostilbene. In other words, when pterostilbene, which is lipophilic, is taken together with resveratrol, which is hydrophilic, it delays the time until it is excreted from the body, allowing it to remain in the body for a longer period of time.

• Because resveratrol has a low bioavailability when taken orally, while pterostilbene has a bioavailability more than four times that of resveratrol, anti-aging dietary supplements containing both NMN and pterostilbene could be very helpful in delaying aging and extending lifespan.

[ Go into detail ]

NMN ( nicotinamide mononucleotide ) was mentioned as a representative key substance that prevents aging and extends lifespan in the book ' Life Span' by Harvard Professor David A. Sinclair .

The three key anti-aging substances mentioned in 'The End of Aging'

NMN, Resveratrol, Metformin

Metformin is a prescription medication prescribed for type 2 diabetes and cannot be used in health functional foods. So, if we take NMN and resveratrol together, can we extend human lifespan and achieve immortality?

NMN is converted to NAD+ within cells and used as fuel for the longevity gene 'Sirtuin', and by increasing NAD+ levels, it helps in cell regeneration, energy activation, and prevention of diseases caused by aging.

Resveratrol, a type of polyphenol commonly found in grapes, blueberries, and raspberries, has been shown to have antioxidant and cardiovascular health benefits. Recent research suggests that resveratrol may help extend lifespan by activating the longevity gene sirtuin.

Therefore, the key is that taking NMN and resveratrol together activates longevity genes and prevents aging.

Why the Pterostilbene + NMN Combination Is More Synergistic Than the Resveratrol + NMN Combination: From a Biochemical Perspective

[Resveratrol chemical structure]

Resveratrol's chemical structure consists of two benzene rings with a hydroxyl group attached. When O-methyltransferase is activated, the hydrogens in the two hydroxyl groups are replaced with methyl groups, transforming it into pterostilbene.

[Pterostilbene chemical structure]

Pterostilbene has a very similar molecular structure to resveratrol, sharing all of its beneficial properties. However, as previously mentioned, the hydrogen from the hydroxyl group in resveratrol's molecular structure is removed and a methyl group is added, increasing its lipophilicity (the property of mixing better with fats). This delays the excretion time of pterostilbene compared to resveratrol, allowing it to remain in the body longer.

Effects of Co-administration of NMN and Pterostilbene on NAD+ Conversion

[A cellular-level perspective on the transformation mechanism of NMN ingested into the body]

If we look at the conversion mechanism of NMN taken into the body from a cellular perspective, the taken NMN is converted into NR outside the cell, and NR enters the cell through the ENT (Equilibrative Nucleoside Transporter ) channel in the cell membrane. NR that has entered the cell is converted back into NMN by the action of the NRK (Nicotinamide Riboside Kinase) enzyme (phosphorylation enzyme), and this is converted into NAD+ through NMNAT (Nicotinamide Mononucleotide Adenylyltransferase).

There is ample evidence that NAD+ plays a crucial role in aging, as it is involved in various biological functions and is a key regulator of stress resistance. NAD+ levels steadily decline with age, leading to altered metabolism and increased susceptibility to disease. (Source: Am J Biomed Sci & Res. 2019 - 6(5)) Therefore, increasing NAD+ levels is key to delaying aging and extending lifespan.

[Mechanism of Pterostilbene on NAD+ Production]

Let's learn about the mechanism by which pterostilbene affects NAD+ production.

Resveratrol and pterostilbene target the SIRT1 enzyme, which in turn activates the AMPK enzyme. AMPK activation stimulates the expression of the gene encoding the NAMPT enzyme, which then mediates a key reaction in the NAD+ salvage pathway, a process that uses the energy of ATP to synthesize NAD+. In cells with low metabolism, increased NAMPT promotes healthy cellular metabolism through a positive feedback loop involving NAD+, which is required for SIRT1 activity.

Additionally, while resveratrol has low bioavailability when taken orally , pterostilbene is lipophilic and less efficiently metabolized, making it four times more bioavailable than resveratrol and allowing it to remain in the body longer .

Based on the above mechanism, when pterostilbene is taken together with NMN , pterostilbene can help convert NMN to NAD+ and allow it to remain in the body longer, thereby achieving optimal anti-aging effects .

source

[1] Evolving concepts in NAD+ metabolism (Cell Metabolism 33, June 1, 2021)

[2] https://www.bioserendipity.com/anti-aging-iii/

[3] https://pubmed.ncbi.nlm.nih.gov/31935877/

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7180342/

[5] https://www.sciencedirect.com/science/article/pii/S0925443915000216