Understanding NAD

By Pit Gills, MD

Nicotinamide adenine dinucleotide, better known as NAD, has received a lot of attention lately. It has sparked both excitement and controversy in the health and wellness world. In this article, I want to break down:

• What NAD actually is
• Why it is essential for every cell in your body
• How NAD changes as we age
•  What is the best way to support NAD

What Is NAD and Why Is It Vital?

NAD is a coenzyme that plays a critical role in every cell. Think of it as the engine oil of your body, it helps everything run smoothly.

NAD has two major roles:

1. Energy Production (ATP Generation)
   • NAD acts as an electron carrier in your mitochondria, constantly converting between NAD and NADH.
   • It is not consumed in this role, it is recycled over and over to fuel your body’s energy production.
2. Cellular Repair and Regulation
   • Here, NAD is consumed as a co-factor in more than 500 enzymatic reactions.
   • These include DNA repair (through PARPs) and the activation of sirtuins, proteins linked to longevity.
   • This connection to sirtuins is what drives much of the conversation around NAD and lifespan.

How NAD Declines with Age

We know that NAD peaks around age 20 and steadily declines over time.

• By age 40, you may have 40 percent less NAD than you did at 20.
• By age 60, you are down by about 60 percent.

NAD levels also fluctuate throughout the day, linked to your circadian rhythm, with peaks often around midday.

This decline is one reason scientists and physicians are so interested in NAD support.

Why You Can’t Just Take NAD Directly

It sounds simple: if NAD declines with age, why not just take more NAD? Unfortunately, it is not that easy.

• NAD is unstable, breaks down quickly, and cannot cross cell membranes.
• That is where NAD precursors come in, forms your body can actually use.

The most common are:

• NR (nicotinamide riboside): Stable and absorbed well, especially in skeletal muscle.
• NMN (nicotinamide mononucleotide): Essentially NR plus a phosphate group.
• NAM (nicotinamide): A breakdown product of NAD that recycles back through the “salvage pathway.”

Research shows that taking oral NR or NMN does increase NAD levels in the body.

Potential Health Span Benefits

While the evidence around lifespan extension remains mixed, there is growing support for health span benefits, including:

• Better mitochondrial function
• Improved insulin sensitivity
• Healthier vascular function
• Support for skin health

One study I find particularly compelling involved 386 patients with a history of skin cancers (non-melanoma). Those who received NAD support for a year had a 23 percent reduction in new skin cancers compared to placebo. However, when supplementation stopped, the benefit disappeared within six months. This suggests NAD support is most effective with consistency.

The Problem with IV NAD

Many people assume IV delivery is always better, but with NAD, that is not the case.

Here is why I do not recommend IV NAD for most patients:

1. NAD cannot enter your cells directly. Instead, it is broken down in the bloodstream, often into NAM, which at high levels can trigger a feedback loop that deactivates sirtuins.
2. NAM can deactivate sirtuins, the very proteins NAD is supposed to activate. The NAM binds to the same receptor NAD would normally bind to on sirtuins.
3. Excess NAM depletes methyl groups, which are crucial for healthy epigenetic function. NAM has a high affinity for methyl groups, and they are needed to get rid of extra NAM.

There may be very specific cases where IV NAD is useful, such as neurological conditions like traumatic brain injury (TBI) or treatment-resistant depression. For most people, oral supplementation is the smarter, safer option.