This is a very common question we get asked at Nuchido. Within the longevity industry the most popular NAD+ supplements include NAD+ the precursors - NMN and NR. NAD+ precursors are the raw material that the body uses to make NAD+. While popular, precursor supplements do not address the causes of NAD+ decline, and when taken in isolation can cause further dysfunction to the NAD+ network. 

Here at Nuchido we take a different approach to boosting NAD+ levels. We appreciate that NAD+ decline as we age is a multi-faceted issue that cannot just be fixed by one ingredient. With a background in cellular aging our scientists have worked for many years studying the best possible formulations to provide long term sustainable benefits. In order to understand how our product differs from a simple precursor we must appreciate what actually occurs to our cellular NAD+ levels as we age.

 

NAD+ decline is complex 

There are two main issues that drive NAD+ decline during aging. 

1. Older cells have reduced NAD+ production - the main NAD+ production pathway in youthful cells is the Salvage Pathway, which recycles waste NAM back into fresh NAD+. The activity of this production pathway declines with age, due to declining levels of the NAMPT enzyme which powers this process.
2. Older cells have increased DNA damage and inflammation which demand more NAD+. 

Collectively this decline in NAD+ production and increase in NAD+ demand create an NAD+ deficit in cells which contributes to the aging process.

Overall, as we age our cells use more NAD+ than they can make or recycle. Therefore, all the repair and maintenance pathways within the cell are fighting over the dwindling supply of NAD+. This leads to many of the signs of aging such as energy loss and increased recovery time.

 

Key Points to remember

• The salvage pathway is the largest producer of NAD+, via recycling waste nicotinamide (NAM) within the cell.
• NAM is, therefore, the preferred precursor of the cell, and the salvage pathway the preferred production pathway.
• NAD+ is a large molecule which cannot cross the cell membrane, so it must be made inside of the cell.

 

The problem with NMN and NR

Now we understand what happens within the cell as we age, lets analyse how NAD+ precursors work. Precursor supplements work by shipping more of the raw material (precursors) into the cells, which it uses to make NAD+. Taking NMN or NR fail to address either of the causes of NAD+ decline. 

NMN and NR do cause a temporary increase in NAD+ levels. However, the increase in NAD+ is limited, as it doesn’t address the underlying reasons why NAD+ declines. The deficit in NAD+ is not because of a lack of precursor material. It is because the cells are using more NAD+ and are unable to recycle the breakdown products.

When large quantities of precursor supplements such as NR or NMN are taken in isolation the initial boost in NAD+ is used by the cell and then the breakdown product NAM is left behind, because the salvage pathway has not been restored the NAM cannot be recycled and accumulates within the cell. Cell's function best at homeostasis (balance) so the excess NAM must be methylated and removed. This can cause methyl donor depletion and leaves other vital processes without sufficient methyl donors.

Precursors also fail to address the increased levels of CD38. This inflammatory molecule is known to increase with age (due to inflammation) and is the largest NAD+ consumer. This means, if CD38 is not inhibited the increased NAD+ levels will be used up and wasted by CD38, potentially fueling further inflammation and cellular damage.

The latest research shows that NAD+ precursors are no longer the best approach to restoring NAD+ levels. We think of them as first-generation NAD+ boosters, they do not address the root causes of NAD+ decline and can actually cause further cellular dysfunction.

We now know the precise parts of the NAD+ network that become altered with age and how to fix them to provide a more sustainable boost in NAD+. That is precisely how Nuchido TIME+ works. 

Nuchido TIME+ uses a whole-system approach

At Nuchido we understand this biological complexity and address it using a whole-system approach. Our unique formulation contains a combination of ingredients that work to fix the root causes of NAD+ decline: 

• Sophora japonica which contains the flavonoids Quercetin, Rutin and Troxrutin for their ability to activate NAMPT (the enzyme which powers the Salvage Pathway). Allowing the cell to recycle NAD+ in the same way youthful cell's do.

• Alpha Lipoic Acid (ALA) for its ability to activate the AMPK pathway. This is the pathway activated by exercise and fasting – which are known to increase NAD+. ALA mimics this and AMPK further activates the NAMPT enzyme to promote NAD+ recycling.

• Parsley leaf contains apigenin which inhibits the activation of CD38. The expression of CD38 increases with age and is known to be one of the main consumers of NAD+.

• Green tea leaf extract contains EGCG for its ability to inhibit NNMT. This enzyme powers the pathway that removes nicotinamide (NAM) from the cell. Now the Salvage pathway has been restored NAM can be recycled back into fresh NAD+, so its removal is inhibited.

• Extra nicotinamide (NAM) as this can now be recycled, to further boost NAD+ levels.

 

 

By using this whole-system approach to restore youthful NAD+ production you can avoid all the issues associated with just taking precursor supplements alone.  

Our clinical trials show that Nuchido TIME+ boosts cellular NAD+, activates NAMPT and SIRT1 which results in lower levels of inflammation, reduction in glycation and reversal of biological age. By restoring cellular health Nuchido TIME+ has whole body benefits including improved energy levels, improved sleep quality and improvements in skin health. 

We hope it is now clear why NAD+ boosting strategies should not just be limited to NAD precursors. A greater NAD+ boost can be obtained with a whole-system approach the tackles the root of the problem.