Beyond a precursor: A New approach to NAD supplementation

Has your body not been able to keep up with you lately? Have you been feeling symptoms that you aren’t as young as you once were? If so and you have identified NAD+ supplementation as a potential solution to your anti-ageing strategy, but are intimidated by the vast amount of choice you are in the right place. To identify which product is best for you we must understand what causes NAD+ decline as we age and why taking a precursor alone isn’t the best solution.

NAD+ and Biological Complexity

In recent years the interest in ageing research has dramatically increased, this abundance of investigation has led to two major discoveries. Firstly, that ageing is a very complex process, involving many different cellular pathways, proteins and feedback systems. Secondly, that ageing isn't a linear process. Meaning we can intervene and stop (hopefully even reverse) the ageing process.

Declining levels of NAD+ have been identified as a key driver in the ageing process. Resulting in many supplements claiming to boost NAD+ levels. These supplements generally focus on NAD+ precursor molecules, such as nicotinamide riboside (NR), nicotinamide mononucleotide (NMN) and nicotinamide (NAM). These precursors are simply the raw materials that your cell needs to manufacture NAD+.

The Lone Precursor Approach doesn’t address the cause of decline

At first glance taking NAD+ precursors alone may seem like a good idea – you are giving the cell more of these raw materials, so in turn it will synthesise more NAD+, right?

Well for that assumption to be correct it would imply that the only reason older cells have less NAD+ is because they don’t have enough raw materials to manufacturer NAD+. Research tells us that isn’t the case. The decline in NAD+ levels as we age is a result of several malfunctioning pathways.

What causes NAD decline as we age?

Ultimately, the age-related decline in NAD+ is due to an increased demand in NAD whilst the cell has a decreased supply of NAD.

The increased demand is due to build-up of inflammation and DNA damage. This age-related inflammation (called inflammaging) is associated with high levels of the CD38 protein which eats up and wastes an awful lot of the NAD+ that the cell makes. The accumulation of DNA damage activates a protein called PARP which helps repair the damage which further uses up the dwindling NAD pool.

The decreased supply is because the cell is unable to produce as much NAD+ as it could when it was young. The salvage pathway is the largest source of NAD+ production within cells, via recycling nicotinamide back into fresh NAD+. The salvage pathways relies mainly on the enzyme NAMPT which unfortunately declines with age. When this occurs the nicotinamide within the cell is methylated signaling that it is to be removed from the cell.

So, not only are older cells using up more NAD+, they also are unable to manufacture NAD+ as efficiently as they once did. The root of the problem isn’t a lack of raw materials so simply pumping the cell with NAD+ precursors will not provide a long-term solution.

To address the root cause of NAD decline with age a whole-systems approach is needed. One which considers each of these factors contributing to NAD decline and addresses them. Only when this approach is taken will a robust increase in cellular NAD+ be achieved.

Learn more about designing better NAD supplements.