What Is NAD+ Therapy? A Plain-Language Overview

NAD+ therapy is one of the most discussed interventions in longevity medicine — but the science behind it is frequently oversimplified or misrepresented. This guide explains what NAD+ actually is, what it does in the body, why it declines with age, and what current evidence says about supplementing it.

What NAD+ Does in the Body

NAD+ operates in two primary roles in cellular biology:

Role 1: Energy Production

NAD+ is a critical cofactor in the mitochondrial electron transport chain — the process cells use to produce ATP from glucose and fatty acids. Without sufficient NAD+, cellular energy production becomes less efficient. This is most noticeable in high-energy-demand tissues: brain, heart, and skeletal muscle.

Role 2: Sirtuin Activation

Sirtuins are a family of proteins that regulate DNA repair, inflammation, stress response, and metabolic efficiency. They require NAD+ to function. As NAD+ declines with age, sirtuin activity decreases — which is thought to contribute to the cellular hallmarks of aging including accumulated DNA damage, increased inflammation, and impaired stress responses.

Other NAD+ Functions

• PARP activation — DNA repair enzymes that detect and repair strand breaks
• CD38 regulation — an enzyme involved in immune function and calcium signaling
• Circadian rhythm regulation — NAD+ synthesis is tied to the body's biological clock
• Neuroprotection — supports brain cell energy metabolism and resistance to oxidative stress

Why NAD+ Declines with Age

Multiple mechanisms drive the age-related decline in NAD+ levels:

• Increased consumption: DNA damage accumulates with age, activating PARP enzymes that consume NAD+ rapidly
• CD38 upregulation: CD38 is an NAD+-consuming enzyme that increases with age and inflammation
• Reduced synthesis: The body's ability to produce NAD+ from dietary precursors (tryptophan, niacin) decreases with age
• Mitochondrial dysfunction: Aging mitochondria are less efficient at NAD+ cycling

This decline is not uniform — lifestyle factors like physical activity, sleep quality, alcohol consumption, and diet all influence NAD+ levels and the rate of decline.

How NAD+ Therapy Works

Because NAD+ is a large molecule that does not cross cell membranes easily, direct supplementation with NAD+ has limited oral bioavailability. Therapeutic approaches work around this in several ways:

NAD+ Precursors (Oral)

The most common approach uses compounds the body converts into NAD+:

• NMN (Nicotinamide Mononucleotide): Directly enters the NAD+ synthesis pathway; good cellular uptake in some tissues
• NR (Nicotinamide Riboside): Converted to NMN and then NAD+; well-studied oral precursor
• Niacin (Vitamin B3): The original NAD+ precursor; effective but causes flushing at therapeutic doses

Direct NAD+ Administration (Injectable/IV)

Subcutaneous injection and IV infusion bypass the absorption limitations of oral delivery. IV NAD+ provides 100% bioavailability and rapidly elevates circulating NAD+ levels. Subcutaneous injection is more convenient and achieves high bioavailability with daily at-home dosing.

What NAD+ Therapy Is Used For

Clinical applications and areas of active research include:

• Fatigue and cellular energy optimization
• Cognitive function and neuroprotection
• Athletic performance and recovery
• Healthy aging and longevity support
• Metabolic health (insulin sensitivity, weight management)
• Addiction recovery support (IV NAD+ has been used in clinical settings)
• Post-COVID recovery protocols

It is important to note that most longevity applications are supported by preclinical data and early human trials rather than large randomized controlled trials. The field is evolving rapidly.

NAD+ Therapy vs Lifestyle Interventions

Frequently Asked Questions

Is NAD+ therapy FDA-approved?

NAD+ is not FDA-approved for any specific disease indication. It is used as a compounded medication prescribed off-label by licensed clinicians for longevity and wellness applications. This does not mean it is unsafe — it means the formal approval process for these indications has not been completed.

How quickly do NAD+ levels respond to therapy?

IV and subcutaneous protocols show measurable increases in circulating NAD+ within hours to days. Oral precursors raise tissue NAD+ levels over weeks of consistent supplementation.

Can I raise NAD+ through diet alone?

Diet provides NAD+ precursors (tryptophan from protein foods, niacin from meat, fish, and legumes), but dietary increases are modest compared to supplementation. Reducing NAD+-depleting behaviors (alcohol, chronic stress, poor sleep) may be as important as adding precursors.

Is NAD+ therapy safe?

NAD+ has a favorable safety profile in human studies to date. Oral precursors are generally well tolerated. IV infusions can cause transient nausea, flushing, or headache if given too rapidly. Subcutaneous injection site reactions are minor and resolve. Long-term safety data for high-dose protocols is still accumulating.

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