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

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

by Rhonda Patrick, Ph.D.

1h 59m•February 9, 2026
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Overview of #109 How To Boost NAD Levels To Fight Inflammation, Improve Recovery, and Slow Aging | Dr. Charles Brenner

This episode is an in‑depth, evidence‑focused conversation between Rhonda Patrick, Ph.D., and Dr. Charles Brenner (discoverer of nicotinamide riboside, NR). They cover NAD biology, why NR is a privileged NAD precursor, clinical evidence that NR reduces inflammation, how lifestyle (obesity, sleep/circadian disruption, chronic inflammation, exercise) affects NAD, practical supplementation guidance (dosing, timing, stacking), safety considerations (cancer concerns, IV NAD myths), and promising clinical targets (peripheral artery disease, fatty liver, long COVID, fertility/lactation). The interview blends mechanistic biochemistry with human trial data and practical takeaways.

Key takeaways

  • NAD is central to energy (NAD+/NADH), biosynthesis/repair (NADP+/NADPH), DNA repair (PARPs), and gene regulation (sirtuins).
  • Nicotinamide riboside (NR) is a clinically tested oral NAD precursor that reliably raises circulating and tissue NAD in humans and animals.
  • Multiple randomized clinical trials (RCTS) show NR has consistent anti‑inflammatory effects in humans at ~500–1,000 mg/day.
  • NR shows promising clinical signals for peripheral artery disease (improved 6‑minute walk), liver fat (underpowered but suggestive), long COVID (within‑group improvements), and brain blood flow in mild cognitive impairment.
  • Lifestyle factors that most stress NAD pools: chronic inflammation (obesity, metabolic disease, alcohol), circadian disruption/poor sleep, and overtraining or acute illness. Exercise increases NAD biosynthetic gene expression and synergizes with NR for recovery.
  • Safety: NR has a favorable safety profile and has been tested up to grams/day in trials; main safety concern is product sourcing/quality (esp. many NMN products and unverified supplements).

What was discussed (topics)

  • Basics of NAD biology: NAD+/NADH and NADP+/NADPH roles; PARPs and sirtuins as NAD consumers.
  • Why NR vs. NMN vs. NAD: phosphate barrier to cell entry; NR is cell‑permeable and well studied; NMN largely converts to NR before getting into cells; oral NAD largely breaks down.
  • Inflammation and infection: SARS‑CoV‑2 and other innate immune triggers drive PARP expression and NAD consumption; NR reduces inflammatory cytokines (IL‑6, etc.) in RCTs.
  • Aging and tissue specificity: blood NAD may not decline universally with age, but tissue NAD pools (liver, heart, brain, cochlea) can be disturbed in disease/aging.
  • Exercise and recovery: exercise upregulates NAD biosynthetic enzymes and mitochondrial biogenesis; NR is widely used anecdotally by athletes for recovery; controlled sport physiology trials are still needed.
  • Circadian biology & timing: NAD synthesis and dependent processes are circadian; taking NR in the morning is logical and commonly practiced; for shift workers take NR at start of their active period.
  • Microbiome: gut bacteria modulate conversion/metabolism of NR/NMN; human data show NR alters microbiome composition and may increase conversion to nicotinic acid derivatives.
  • Pregnancy, lactation & offspring: strong mouse data — maternal NR increased milk production and offspring lean mass, neurogenesis, and behavior; human trials (especially for preemies/lactation) are being planned but human safety data are limited.
  • IV NAD/NMN drips: commercial NAD “IV therapies” often break down into NR/smaller molecules; IV NR exists but oral NR has the strongest clinical evidence to date.

Evidence & clinical findings (high‑value results)

  • Anti‑inflammatory RCTs: ~8 randomized trials report NR lowers inflammatory markers (e.g., IL‑6). Effective clinical dose commonly 500–1,000 mg/day.
  • COPD sputum inflammation: NR reduced inflammatory markers in sputum in RCT where inflammation was the primary endpoint.
  • Peripheral artery disease (McDermott et al.): NR improved 6‑minute walk distance vs. placebo (NR+resveratrol arm did not improve — resveratrol appeared to block NR benefit).
  • Long COVID: recent within‑group improvements reported (not yet strong randomized superiority evidence) — promising but requires more RCT data.
  • Brain: small studies show oral NR increases brain NAD and improves cerebral blood flow in mild cognitive impairment.
  • Liver: human trial showed a substantive absolute reduction in liver fat in NR arm, but result missed statistical significance due to variability and underpowering — suggests targeted trials (randomized for fatty liver) are warranted.
  • Safety signals: nicotinamide (classic NAD precursor) reduced nonmelanoma skin cancer incidence in large Australian trials; NR safety profile is reassuring in trial data; NR tested up to ~3 g/day in some contexts.

Mechanisms (how NAD and NR work)

Major NAD roles

  • Energy transfer: NAD+ accepts electrons from food → NADH, feeds electron transport/ATP production.
  • Biosynthesis & repair: NADPH supports anabolic reactions (lipid, nucleotide synthesis) and ROS detoxification.
  • DNA repair signaling: PARP enzymes consume NAD to ADP‑ribosylate proteins and recruit DNA‑repair machinery.
  • Gene regulation & signaling: Sirtuins use NAD to remove acyl groups from proteins, affecting gene expression and metabolism; other NAD‑consuming enzymes regulate calcium signaling, etc.

Why NR is often preferred

  • NR is a nucleoside without phosphate, so it can enter cells and be phosphorylated inside via NR kinases (NMRK1/2).
  • Certain diseased tissues upregulate NMRK pathways and thus prefer NR (e.g., failing heart).
  • NMN has a phosphate and largely converts back to NR extracellularly before cell uptake; many commercial NMN products lack consistent verification.

Practical guidance (what to do / how people use NR)

  • Typical human RCT dosing: 500–1,000 mg/day of NR (split or single dose); clinical effects on inflammation often seen in this range.
  • Timing: morning dosing recommended to align with circadian biology and active metabolic period; for shift workers take at start of active/wake period.
  • Pairing with lifestyle: prioritize weight loss if obese, improve sleep/circadian alignment, and exercise (resistance + aerobic as tolerated). Exercise + NR appears synergistic for recovery and mitochondrial adaptation.
  • Athletes & recovery: widespread anecdotal use in pro/college teams for recovery; controlled trials in exercise physiology are needed.
  • Testing NAD: commercial NAD testing (e.g., NADMED) can be useful in clinical trials but is of limited value for most consumers—if you take a quality NR product, it reliably raises NAD for most people.
  • Avoid blind stacking: resveratrol/terostilbene can block or negate NR benefits in certain contexts (resveratrol blocked benefit in PAD trial; terostilbene may increase LDL). Don’t assume polyphenol “boosters” always help.

Safety, sourcing & contraindications

  • Sourcing matters: many supplements — especially NMN from non‑verified vendors — may not contain the claimed material or may be contaminated. Use clinically‑tested, third‑party‑verified products (NSF, etc.).
  • Cancer concerns: population RCTs with nicotinamide showed reduced skin cancer risk — clinical evidence does not indicate cancer‑promoting effects at population level. Mouse/cell studies can be misleading; if you have active cancer or are on chemo, consult your oncologist before supplementing.
  • Dosing ceiling: NR has been safety tested (some trials up to grams/day); Dr. Brenner advises most people should not exceed trialed/safe product ranges and recommends ~500–1,000 mg/day for common uses; some testing has used higher doses but avoid extreme self‑experimentation.
  • IV NAD/NMN: oral NR has the largest evidence base. Injected NAD is commercially promoted but often causes innate immune activation and is not clearly superior; IV NR is being explored but clinical data are limited.
  • Pregnancy & lactation: no human safety data yet — animal data show benefits (increased milk and improved offspring outcomes). Human lactation/preemie studies are being planned; pregnant people should consult their physician.

Open questions & research needs

  • Tissue‑specific NAD declines in aging: more human tissue studies (liver, brain, muscle, adipose) are needed to map NAD changes with age and disease.
  • Optimal dosing/timing in different populations (athletes, shift workers, pregnant/lactating women).
  • Mechanistic links: clearer human data tying NR’s anti‑inflammatory effects to functional outcomes (cognition, fatigue, infection risk).
  • IV vs oral biodistribution: how best to deliver NR/NAD for specific organ targeting.
  • Microbiome interactions: human trials exploring how gut microbes affect NR/NMN conversion and downstream benefits.

Actionable recommendations (concise)

  • Prioritize lifestyle first: reduce chronic inflammation via weight loss (when indicated), better sleep/circadian alignment, and exercise.
  • Consider NR supplementation if you have high inflammatory burden, need improved recovery from intense training, or are in a population with promising evidence (e.g., PAD, liver disease under study, long COVID). Typical clinical range: 500–1,000 mg/day.
  • Take NR in the morning (or at the start of your active period if you are a shift worker).
  • Use third‑party‑tested, clinically studied NR products (avoid unverified NMN or unlabeled products).
  • If you have active cancer, are undergoing chemo, are pregnant, or have complex medical issues, consult your clinician before starting NR.

Notable quotes and insights

  • “NAD coenzymes are the wiring for high‑energy electrons in biology — they let us direct energy into processes rather than letting the energy go up in smoke.”
  • Dr. Brenner: NR is uniquely useful because certain stressed/diseased tissues upregulate NR kinases and “are looking for the nucleoside” (NR) to rebuild NAD.

Useful resources mentioned

  • Brenner lab: BrennerLab.net
  • NR clinical/safety context: Niagen (product history) and NADMED (clinical NAD testing company)

Summary closing This episode provides a practical, evidence‑anchored primer on NAD biology and nicotinamide riboside. It balances mechanistic detail with trial results and pragmatic guidance: lifestyle changes remain primary; NR is a well‑studied, generally safe NAD precursor with clear anti‑inflammatory effects and several promising clinical applications, but product quality, individual medical context, and appropriate trial design matter.