#109 How To Boost NAD Levels To Fight Inflammation, Improve Recovery, and Slow Aging | Dr. Charles Brenner

What It Covers

Dr. Charles Brenner, discoverer of nicotinamide riboside, explains NAD biology and its role in cellular energy, DNA repair, and inflammation. The discussion covers clinical evidence for NR supplementation at 500-1000mg daily, how chronic inflammation and disease states deplete NAD, safety considerations including cancer risk, and practical strategies for supporting NAD through lifestyle factors like exercise, sleep timing, and circadian rhythm optimization.

Key Questions Answered

• •Anti-inflammatory effects: Eight randomized controlled trials demonstrate nicotinamide riboside at 500-1000mg daily significantly lowers inflammatory markers including IL-6 and IL-10 in humans. The effect proves strong enough that participants receiving NR first in crossover trials maintained lower inflammation three weeks after switching to placebo. This anti-inflammatory action appears most beneficial for individuals with elevated baseline inflammation from conditions like obesity, COPD, or metabolic dysfunction.
• •Blood versus tissue NAD: Blood NAD levels remain relatively stable with age in healthy individuals at approximately 20 micromolar, but tissue NAD in organs like liver, brain, and muscle declines significantly. People with mitochondrial disease show measurably lower blood NAD, while inflammatory conditions tax NAD systems across multiple organs simultaneously. This explains why blood testing provides limited value for individuals—supplementation reliably increases NAD regardless of baseline measurements.
• •Peripheral artery disease improvement: A three-arm clinical trial in peripheral artery disease patients showed NR alone improved six-minute walk test performance over six months, while placebo and NR plus resveratrol groups both declined. The resveratrol combination actually blocked NR benefits, demonstrating no use case for combining these compounds. This represents one of the strongest medical indications for NR in age-related disease, with larger trials currently underway.
• •Exercise recovery mechanism: Professional sports teams and college athletic programs use NR supplementation based on training data showing improved recovery, though rigorous placebo-controlled trials remain limited. Exercise increases gene expression of NAD biosynthetic enzymes, creating synergy between physical activity and supplementation. The optimal approach combines regular exercise as standard practice with NR supplementation rather than expecting NR alone to improve performance without training.
• •Maternal and offspring benefits: Pregnant mice supplemented with NR produced more milk and transferred more calories during lactation, resulting in offspring with better lean mass at weaning that persisted lifelong. These offspring demonstrated faster physical development, improved balance beam performance, lower anxiety behaviors, and enhanced adult hippocampal neurogenesis. UC Davis researchers now plan human trials with mothers of premature infants who typically struggle to produce adequate milk.
• •Circadian timing matters: NAD synthesis and NAD-dependent metabolic processes follow strong circadian rhythms, with disruption from shift work or jet lag disturbing the NAD system. Supplementation should align with circadian biology—taking NR in the morning mimics natural nutrient intake patterns since micronutrients and macronutrients enter cells together during meals. For shift workers, this means taking NR at the start of their work cycle regardless of clock time.
• •Cancer safety profile: Large randomized trials in Australia demonstrate nicotinamide supplementation lowers nonmelanoma skin cancer risk at the population level, establishing that NAD boosting does not cause cancer. While some cell line and mouse tumor models suggest NAD could theoretically limit certain established tumors, this does not translate to human cancer development. The clinical evidence hierarchy places large human trials above artificial tumor models for safety assessment.