There is no known optimal balance of NAD+ to NADH and there is an uneven balance between the two.
Researchers and scientists believe that it is not how much NAD+ in our bodies which determines how healthy we are, but the ratio of NAD+ to NADH.
The ratio between both NAD+ and NADH determines how effectively the cell can produce ATP and that ratio is determined from the body’s requirements which can impact cellular health.
In the cell, the ratio between NAD+ & NADH will vary in certain places which were shown in a study that the NAD+ to NADH ratio varied in the mitochondria & cytoplasm of the liver of mice.
The cytoplasm was depleted under stress whereas the mitochondria protected itself from stressors.
Even when NAD+ levels were extremely drained, the levels of NAD+ in the mitochondria remained the same for up to 3 days - possibly due to the inability of NAD+ to cross the membrane of the mitochondria which acts as the entry door to the mitochondria.
The levels of NAD+ to NADH in the mitochondria will only be compromised when the cells are in extreme distress and the membrane is compromised.
To create more energy in your body, a higher ratio would be preferable with a study showing NAD+ levels decreasing with age and NADH levels increasing with age.
This has led to an increase in the popularity of supplements that act as NAD precursors such as Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN).
Sirtuins are enzymes which consume NAD+ to function efficiently. However, they are not redox reactions and don’t convert to NADH when they use NAD+; instead, they divide NAD+ to create Nicotinamide.
The nicotinamide formed by sirtuins has to be recycled along pathways called the salvage pathways to turn back into NAD+