How To Boost NAD Levels To Fight Inflammation, Improve Recovery, and Slow Aging

February 10, 2026 1h 54m

Found My Fitness

Key Takeaway

NAD (nicotinamide adenine dinucleotide) is critical for converting fuel, building cellular components, and repairing damage. While blood NAD levels may remain stable with age, tissue-specific NAD becomes depleted through chronic inflammation, metabolic dysfunction, and disrupted circadian rhythms. The most actionable insight: Address the root causes of NAD depletion—obesity, chronic inflammation, poor sleep—through lifestyle changes like exercise and weight loss before relying solely on supplements.

Episode Overview

Dr. Charles Brenner, discoverer of nicotinamide riboside (NR) as an NAD precursor, discusses NAD biology with a focus on evidence-based science. The episode explores how NAD levels decline in specific tissues (not necessarily blood) due to inflammatory processes, metabolic disease, and lifestyle factors. Dr. Brenner explains that eight randomized controlled trials show NR supplementation has anti-inflammatory benefits, particularly in conditions like COPD and long COVID. Key topics include: • The difference between blood NAD and tissue NAD levels • How inflammation, obesity, and sleep disruption tax the NAD system • Exercise's role in boosting NAD biosynthetic enzymes • Why lifestyle interventions should precede or accompany supplementation

Key Insights

Blood NAD Doesn't Tell the Whole Story

Human blood NAD levels typically remain stable at around 20 micromolar even with aging. However, tissue-specific NAD (in liver, muscle, brain, cochlea) can decline significantly with disease states like alcoholism, mitochondrial disorders, and noise-induced hearing loss. Blood measurements don't necessarily reflect what's happening in critical organs.

Inflammation Is a Major NAD Consumer

Viral infections like COVID-19 activate five different members of the PARP (poly ADP-ribose polymerase) superfamily, which consume NAD as part of the innate immune response to double-stranded RNA. This inflammatory process depletes NAD reserves across multiple tissues, explaining why conditions with chronic inflammation systematically disturb the NAD system.

Obesity Creates an NAD 'Perfect Storm'

In mice fed high-fat diets pushed to type 2 diabetes, the liver NAD system becomes disturbed with NADPH at the center. These animals face increased reactive oxygen species that consume NADPH faster than it can be regenerated. The mechanism isn't reduced NAD synthesis—it's excessive consumption that the body can't keep pace with.

NR Supplementation Shows Robust Anti-Inflammatory Effects

Eight randomized controlled trials demonstrate that nicotinamide riboside (around 1 gram daily) has anti-inflammatory effects in humans, significantly lowering IL-6, IL-10, and other inflammatory markers. One trial showed effects persisting 3 weeks after stopping NR. This benefit appears strongest in people with existing inflammatory conditions like COPD and long COVID.

Exercise Upregulates NAD Biosynthesis Genes

Clinical evidence shows exercise increases gene expression of NAD biosynthetic enzymes. This aligns with exercise's role in promoting mitochondrial biogenesis and metabolic pathways associated with youth. The exercise you actually do is infinitely more valuable than what you plan to do—any movement beats none.

Circadian Disruption Disturbs NAD Systems

Young mice with strong chronosynchrony have healthy NAD systems, while older mice losing circadian rhythm show NAD system disturbances. Many NAD synthesis processes and NAD-dependent metabolic functions follow time-of-day cues, making chronic sleep disruption or frequent time zone changes likely to disturb NAD metabolism.

Notable Quotes

"Converting fuel, building stuff, and repairing stuff. Those are the buckets in which NAD co-enzymes are critical."

— Dr. Charles Brenner

"I don't think that there's evidence that human blood NAD declines in age. I think that the likelihood that a number of human tissue NAD pools decline or are disturbed in age is incontrovertibly true."

— Dr. Charles Brenner

"We published a paper in 2020 on the effect of corona virus infection not just on mouse liver but on human lung samples... we found five different members of the PARP super family that were transcriptionally activated by corona virus infection."

— Dr. Charles Brenner

"We know as for a fact... there are eight trials showing anti-inflammatory activity in human RCTs... NR lowers those inflammatory markers. Placebo doesn't."

— Dr. Charles Brenner

"You know that the exercise that you do is infinitely better than the exercise that you plan to do or wish you did."

— Dr. Charles Brenner

Action Items

1
Prioritize Treating Root Causes of NAD Depletion
If you have obesity, chronic inflammation, or sleep issues, address these through weight loss (including GLP-1 medications if appropriate), improved sleep hygiene, and stress management before or alongside NAD supplementation. These lifestyle factors are primary drivers of tissue NAD depletion.
2
Incorporate Regular Exercise for NAD Support
Engage in consistent physical activity—any form you'll actually do. Exercise upregulates NAD biosynthetic enzyme expression and promotes mitochondrial biogenesis. Professional athletic programs report NR helps with recovery, suggesting a synergistic effect between exercise and NAD precursors.
3
Consider NR Supplementation if You Have Inflammatory Conditions
If you have conditions associated with chronic inflammation (COPD, long COVID, metabolic syndrome), nicotinamide riboside at approximately 1 gram daily has demonstrated anti-inflammatory benefits in eight randomized controlled trials. This appears most beneficial for those with existing inflammatory burden.
4
Stabilize Your Circadian Rhythm
Maintain consistent sleep-wake times and minimize time zone disruptions when possible. NAD synthesis and NAD-dependent processes follow circadian cues. Chronic circadian disruption likely disturbs tissue NAD systems even if blood levels appear normal.