NAD+ has gained a lot of well-deserved attention recently, but with so many different products to choose from, it is important to understand what the latest scientific research shows. Excitingly, studies have uncovered the precise causes of NAD+ decline during aging, meaning these cellular changes can be addressed to boost NAD+ and promote cellular health. This article will look at why NAD+ declines during aging, how the Nuchido TIME+ formulation works to address these changes and how we are different from other products such as NAD+ supplements, IVs, patches and injections.
Why does NAD+ decline?
So, let’s break down why NAD+ declines during aging. Overall, it can be summarised as a decline in NAD+ production and an increase in NAD+ consumption which leaves critical cellular processes without sufficient NAD+, as shown below.
Decreased production - NAD+ is a large molecule so where possible, cells prefer to recycle it rather than make it entirely from scratch. The main source of NAD+ in your body is from the ‘Salvage Pathway’, this is the cells NAD+ recycling pathway.
When NAD+ is used up in energy production, cellular maintenance and repair pathways it leaves behind the waste product nicotinamide (NAM). This nicotinamide is then recycled back into fresh NAD+ via the salvage pathway so that it can be used again. When we are young, our NAD+ levels are high because the salvage pathway works efficiently, meaning our cells can make and recycle all the NAD+ they need.
As we get older, NAD+ levels decline due to the loss of NAD+ recycling. This occurs because the activity of the enzyme which powers the Salvage Pathway, called NAMPT declines with age, meaning less NAD+ is recycled.
When this happens the waste NAM accumulates in the cell as it cannot be recycled. Cells work optimally when there is ‘homeostasis’ (when everything is in balance), so they must methylate and remove the excess NAM from the cell, which can lead to methyl donor depletion.
Increased consumption - Alongside this decline in NAD+ recycling, there is also an increased demand for NAD+ in older cells due to increased levels of inflammatory CD38.
One of the key hallmarks of aging is ‘inflammaging’. This occurs when the immune system creates inflammation even when it isn’t needed. If this occurs for long periods of time it can lead to ‘chronic inflammation’, in which the pro-inflammatory pathways are constantly active. Chronic inflammation causes damage to cells, tissues and organs preventing them from functioning optimally.
Increased inflammation in the body is known to deplete NAD+ levels, this is because it causes increased expression of a molecule called CD38. CD38 is the largest consumer of NAD+, it wastes around 100 molecules of NAD+ for every reaction it performs. It also has a higher affinity for NAD+ than other beneficial pathways that rely on NAD+ such as the sirtuins. This means the reduced NAD+ available in older cells is wasted by inflammatory pathways rather than being directed towards energy production or cellular repair, which further accelerates cellular aging.
Overall, this creates the perfect storm, causing an NAD+ deficit within the cells.
Nuchido TIME+ restores youthful NAD+ production
When choosing a method to boost your NAD+ levels it is therefore important to choose a product which addresses these root causes of NAD+ decline.
This is exactly how the Nuchido TIME+ formulations works. Nuchido TIME+ doesn’t just throw more raw materials into the cell such as NR or NMN in the hope that it will be converted into NAD+ and it doesn’t include whole NAD+ which struggles to enter most cells and is very unstable. Instead, our combination of ingredients targets each specific part of the NAD+ network which is known to cause NAD+ decline during aging as in the table below.
NAD+ decline is a complex problem; therefore, one singular ingredient will likely never produce the best result. That is why we use a ‘whole-system’ approach. We look at the entire NAD+ network and target each part listed above that becomes dysfunctional with age.
While other products may simply put a plaster on the problem of NAD+ decline, Nuchido TIME+ goes beyond this to fix the root causes and restore the cell’s youthful ability to make NAD+.
Nuchido TIME+ is supported by clinical evidence
Our unique whole-systems approach is supported by clinical data. We conducted a randomised, double-blinded, placebo-controlled crossover clinical trial on Nuchido TIME+. Participants were male and female, aged 20-80 years old.
The results of our study showed that after 28 days of supplementation Nuchido TIME+:
- Significantly increases cellular NAD+ after only 7 days
- Unlike NR or NMN it works by switching back on youthful cellular NAD+ production by reactivating NAMPT, a key enzyme in the Salvage Pathway
- The increase in NAD+ also caused an increase in the longevity protein SIRT1, a downstream target of NAD+
- A reduction of inflammatory cytokines indicating that NAD+ is being directed towards beneficial processes rather than inflammatory CD38
- A reduction in biomarkers of glycation another hallmark of aging
Collectively the increased NAD+ and downstream benefits, such as activation of SIRT1 and reduced inflammation caused a reversal of biological age by 1.26 years indicating the rate of cellular aging is decreasing as Nuchido promotes cellular health.
What is the difference between NAD+ IVs, precursors, or injections?
Other popular methods to boost NAD+ levels are precursor supplements such as NR or NMN. These are the raw materials used to make NAD+ inside the cell. We refer to these as first-generation NAD+ boosters because they were the first products created to try and boost NAD+ levels. The problem with precursors is that they do not fix the causes of NAD+ decline - there is simply no evidence that NAD+ declines because of a lack of precursor material. Precursors also require transporters to enter cells and studies show that not all cells have these.
When ingested, precursor supplements may cause a slight increase in NAD+ levels but once the NAD+ is used the waste NAM is left behind and cannot be recycled. This can further disrupt cellular homeostasis and can cause methyl donor depletion. This is damaging because methyl donors are critically important for a multitude of cellular reactions. Additionally, because these products fail to address increased inflammation in the body, it is likely that the majority of the NAD+ increase will be consumed by CD38, further driving inflammation
The other popular method is taking ‘pure’ NAD+ via an intravenous infusion (IV), injection or patch. While this may sound like a promising approach because it gets the NAD+ directly into your blood, NAD+ has little function in the blood as it performs its beneficial role inside the cells. As NAD+ is a large molecule, to access the cells it requires a specific transporter channel and the only cells which have been shown to possess this channel are heart and brain cells. Despite the popularity of these methods, there is a distinct lack of clinical data to prove NAD+ IVs, injections or patches perform as advertised. Finally, putting such large quantities of NAD+ directly into your body means your body then must work very hard to break it down and remove the waste. This is why people often report feeling nauseous or unwell when getting an NAD+ IV.
The table below gives an overview of how each of these products works.
NAD+ restoration is a critical component to support healthy aging and the data highlight NAD+ decline is a complex issue. Therefore, the best approach to increasing NAD+ levels is to fix the reasons why it declines. This is not possible by taking precursor supplements or pure NAD+. A multitarget approach such as Nuchido TIME+ is needed and is supported by clinical data.
Conlon, N., & Ford, D. (2022). A systems-approach to NAD+ restoration. Biochemical pharmacology, 198, 114946.