NAD molecule illustration representing cellular energy, mitochondrial function, and anti-aging therapy — Age-X Clinics

What is NAD+, and why you should take it?

November 27, 20254 min read

What Is NAD and What Is the Best Way to Supplement It ?

Nicotinamide Adenine Dinucleotide (NAD) is an essential coenzyme found in every living cell. It participates in over 300 cellular reactions and plays a central role in:

  • Energy production (ATP synthesis)

  • DNA repair and cellular regeneration

  • Mitochondrial function

  • Sirtuin activation (anti-aging pathways)

  • Redox reactions and antioxidant defense

NAD functions as a key electron carrier during oxidative phosphorylation in the mitochondria. Without sufficient NAD, cells cannot efficiently convert nutrients into ATP—the body’s primary “energy currency.”

Why NAD Declines With Age

NAD levels naturally decrease by 40–60% between ages 40 and 60 due to:

  • Increased inflammation (activating CD38, a major NAD-consuming enzyme)

  • Oxidative stress

  • Mitochondrial dysfunction

  • Greater demand for DNA repair

  • Decreased endogenous synthesis

This decline is strongly associated with metabolic dysfunction, fatigue, decreased cognitive performance, and accelerated aging.

Potential Health Benefits of Optimizing NAD

Research—both human and translational—suggests that maintaining optimal NAD levels may support:

1. Brain & Cognitive Health

  • Enhances neuronal energy metabolism

  • Slows age-related cognitive decline

  • Supports neuroprotection (via SIRT1 and SIRT3)

Key evidence: NR increased NAD in the brain and improved cognitive markers in older adults (Brady et al., 2022).

2. Chronic Fatigue & Mitochondrial Support

Higher NAD availability improves mitochondrial ATP production and may reduce fatigue seen in:

  • Chronic fatigue states

  • Long COVID

  • Age-related energy decline

Key evidence: IV NAD increased energy and mitochondrial function markers in small clinical trials.

3. Metabolic and Cardiovascular Health

NAD precursors show benefits for:

  • Insulin sensitivity

  • Fat oxidation

  • Lowering triglycerides

  • Improving endothelial function

Key evidence: NR improved lipid parameters and reduced inflammatory cytokines (Martens et al., 2018).

4. Anti-Aging & Cellular Repair

NAD activates sirtuins, PARPs, and other longevity-associated enzymes:

  • DNA repair

  • Reduced oxidative damage

  • Improved autophagy and mitophagy

  • Maintenance of telomere integrity

5. Inflammation & Immune Modulation

Acts as a cofactor for enzymes involved in cellular defense and immune regulation.

Key evidence: NAD repletion showed anti-inflammatory effects in human macrophages and in vivo models.

Clinical Uses of NAD in Functional & Regenerative Medicine

Common NAD-related clinical applications include:

  • Anti-aging protocols

  • Chronic fatigue and mitochondrial dysfunction

  • Cognitive decline / neuroprotection

  • Metabolic optimization (insulin resistance, obesity)

  • Alcohol or drug detox support (under physician supervision)

  • Adjunct therapy for neurodegenerative conditions (Alzheimer’s, Parkinson’s—experimental)

Age-X Clinics often use a combined strategy: IV NAD for rapid restoration + oral precursors for maintenance.

What Is the Best Way to Supplement NAD?

There is no single “best” option—each has specific benefits. The most studied NAD precursors are:

1. NMN (Nicotinamide Mononucleotide)

Pros:

Direct precursor to NAD

  • Strong evidence in metabolic health and cellular aging

  • Good oral bioavailability

  • Rapid conversion into NAD

Evidence:

NMN improved muscle insulin sensitivity in postmenopausal women (Yoshino et al., 2021).

Best for: anti-aging, metabolic support, mitochondrial health

2. NR (Nicotinamide Riboside)

Pros:

  • FDA-recognized as GRAS

  • Well-studied in humans

  • Improves NAD in blood and tissues

  • Potential cognitive benefits

Limitations: conversion to NMN required before reaching NAD.

Evidence:

NR improved blood pressure and arterial health in older adults (Martens et al., 2018).

3. NAD IV Therapy

Pros:

  • Immediate elevation of systemic NAD

  • Can achieve higher levels than oral supplements

  • Useful in clinical settings: fatigue, detox, neuro support

Limitations:

  • Must be administered by trained clinicians

  • Time-intensive (60–180 minutes)

Best for: patients seeking rapid NAD restoration.

4. Niacin (Vitamin B3)

Effective but limited by flushing and GI side effects.

So Which Is the Best? (Clinically)

For longevity and metabolic optimization, most practitioners—including many in regenerative medicine—prefer:

→ Daily NMN or NR (for long-term maintenance)

→ Periodic IV NAD (for rapid elevation or therapeutic use)

Age-X Protocol Example:

  • IV NAD 250–500 mg monthly or as needed

  • NMN 300–500 mg/day (or NR 300–600 mg/day) for maintenance

  • Combine with sirtuin-activating lifestyle factors: exercise, fasting, red/infrared light therapy

At Age-X clinics we will help you to restores your NAD+levels and boost your energy and metabolism to increase your lifespan and most importantly your healspan, call us at

813-751-3570 for the Apollo Beach office

940-303-4120 for the Bradenton office,

References (Clinically Relevant & High-Quality)

  1. Martens CR et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD in healthy middle-aged and older adults. Nat Comm. 2018.

  2. Yoshino M et al. NMN increases muscle insulin sensitivity in prediabetic women. Science. 2021.

  3. Brady NN et al. Nicotinamide riboside increases brain NAD and improves neurodegeneration biomarkers. Aging Cell. 2022.

  4. Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD boosting strategies in aging and disease. Nat Rev Drug Disc. 2018.

  5. Verdin E. NAD in aging, metabolism, and neurodegeneration. Science. 2015.

  6. Poddar SK et al. NAD and mitochondria: implications in aging and disease. Cell Metabolism.

  7. CD38 and NAD depletion research: Chini CC et al. Trends Mol Med. 2018.

Dr. Al W. Robaina, MD, is a leading expert in anti-aging and regenerative medicine at Age-X Clinics. With over 20 years of experience helping patients optimize longevity, vitality, and cellular health, Dr. Robaina combines medical science with holistic lifestyle strategies to help you look, feel, and perform your best at any age.

Dr. Al W. Robaina, MD

Dr. Al W. Robaina, MD, is a leading expert in anti-aging and regenerative medicine at Age-X Clinics. With over 20 years of experience helping patients optimize longevity, vitality, and cellular health, Dr. Robaina combines medical science with holistic lifestyle strategies to help you look, feel, and perform your best at any age.

Instagram logo icon
Back to Blog

Copyright © 2025 | Age-X Clinics | All Rights Reserved.