What’s the difference between NAD vs NAD+

NAD is a collective term, it stands for Nicotinamide Adenine Dinucleotide. It represents all forms that NAD takes in various chemical processes in the human body. However, supplements may list NAD or NAD+ as the active ingredient. So, is there any difference between NAD and NAD+? The answer is both yes and no.

Whenever the term NAD is used, it refers to the body’s processing of NAD and not to a particular molecule. When referring to ‘NAD’ as an active ingredient in supplements, in the body it can be found in two different molecular structures, one is NADH and the other is NAD+.

The Transformation Process

NADH and NAD+ essentially denote the same chemical (NAD) that is transformed between different molecular structures. To understand the process, it is best to consider the role of NAD in the mitochondria. The mitochondria are often referred to as ‘the powerhouse of the cell’ and their function is to produce energy for the proper functioning of cells. NAD provides the necessary fuel for the mitochondria to function. Therefore, it can be said that NAD is an essential component in the body’s energy-production process.

NAD is initially introduced into the energy cycle as NAD+. NAD+ can be considered the raw form of NAD and acts as a vehicle for delivering essential components to the cells. As an analogy, the creation of NAD+ is the equivalent of manufacturing the body of a truck, when produced it does not contain any cargo in its bed. However, the driver can use the cargo space required to deliver goods. In this way, the body can use NAD+ to ferry necessary components to the cell enzymes, including mitochondrial enzymes.

NADH can be considered the processed, or ‘loaded’ form of NAD+. Using our truck analogy, NADH is a truck with cargo. NADH is an NAD+ molecule carrying a negatively charged hydrogen ion (a hydrogen molecule with two electrons). The primary purpose of NADH is to carry the electrons to the mitochondrial enzymes. In the absence of NAD+, the mitochondria would not receive ions and there would be no energy-making process.

It is worth noting that NADH does not have the ‘+’ sign. This is because the charged hydrogen ion cancels the positive charge of the NAD+ molecule. Once NADH approaches the enzymes, they drop off the charged electrons and eject the hydrogen atom, becoming NAD+ once again. The cell enzymes manage the rest from there. NAD+ becomes an empty truck after the drop-off and is recycled to collect and deliver more hydrogen ions to the cells.

As we age our bodies become less able to effectively recycle the consumed NADH back into NAD+, which leads to depleted NAD+ levels. The lack of new NAD+ means the body cannot continue to provide the mitochondria with the necessary resources for healthy operation. This can lead to compromised mitochondria function resulting in damaged mitochondria, reduced energy and other age-related issues.

The Overall Process

As the NAD+ molecule receives and then delivers electrons to the mitochondria, it constantly changes back and forth between NADH and NAD+. Because of this ongoing process, the molecular structure of NAD in the body depends on the current stage in the process. As we age our bodies cannot recycle NADH back into NAD+ and this causes a lowering of the body’s NAD+ to NADH ratio.

The key question is, what ratio of NAD+ does the body require compared to NADH? While the ideal ratio is not precisely known, research has demonstrated that a higher NAD+ to NADH ratio is favourable. More specifically, it has been found that low NAD+ to NADH ratios are associated with mitochondrial complications and early aging.

Brandauer et al. (2013). AMP-activated protein kinase regulates nicotinamide phosphoribosyl transferase expression in skeletal muscle. J Physiol. 2013 Oct 15;591(20):5207-20. doi: 10.1113/jphysiol.2013.259515. Epub 2013 Aug 5.

Titov DV et al. 2016. Complementation of mitochondrial electron transport chain by manipulation of the NAD+/NADH ratio. Science. 2016 Apr 8;352(6282):231-5. doi: 10.1126/science.aad4017.