FoundMyFitness

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

February 9, 2026

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  • Human blood NAD levels do not universally decline with age, but tissue NAD pools are likely disturbed by age-related disease states like obesity and chronic inflammation. 
  • Nicotinamide Riboside (NR) has robust clinical evidence supporting its anti-inflammatory benefits in humans at doses between 500 to 1,000 milligrams daily. 
  • Oral NAD precursors like NR can increase brain NAD levels, and NR supplementation has shown potential benefits in conditions like mild cognitive impairment and peripheral artery disease, while direct oral NAD supplementation is ineffective because the molecule cannot enter cells. 
  • Human clinical data suggests Nicotinamide Riboside (NR) supplementation may significantly reduce hepatic (liver) fat, although statistical significance was not reached in one trial due to high variability in baseline liver fat. 
  • For healthy individuals, the best argument for supplementing with an NAD precursor like Nicotinamide Riboside is likely enhanced workout recovery, as it synergizes well with exercise. 
  • The primary safety concern for NAD precursors is the sourcing and purity of the supplement, as many commercially available products may not contain the clinically tested material or could contain contaminants. 

Segments

Introduction and Guest Context
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(00:00:00)
  • Key Takeaway: Dr. Charles Brenner is the leading global expert on NAD biology and the discoverer of nicotinamide riboside (NR).
  • Summary: Dr. Charles Brenner, a distinguished biochemist, discovered nicotinamide riboside (NR), a potent vitamin precursor to NAD. NAD is fundamental to cellular energy, DNA repair, gene regulation, and immunity. The episode promises an in-depth, evidence-based discussion on NAD mechanisms and boosters.
NAD Levels and Aging Debate
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(00:05:36)
  • Key Takeaway: Human blood NAD levels do not reliably decline with age, though tissue NAD pools are likely disturbed by disease.
  • Summary: The premise that human blood NAD declines universally with age is overstated; data shows normal levels in healthy older individuals. Low blood NAD is primarily observed in specific conditions like mitochondrial disease. Tissue NAD levels, however, are incontrovertibly disturbed by age and disease states.
Coronavirus Impact on NAD
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(00:10:20)
  • Key Takeaway: Coronavirus infection transcriptionally activates five members of the PARP superfamily, consuming NAD resources.
  • Summary: Innate immune response to viral double-stranded RNA involves immediate activation of PARP enzymes. This activation consumes NAD, linking infection directly to NAD system disturbance. This mechanism is a common response to invaders like double-stranded RNA and endotoxin.
Dietary Precursors and Blood NAD
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(00:13:34)
  • Key Takeaway: Substantive intake of NAD precursor vitamins (300mg+) causes measurable changes in the circulating NAD metabolome.
  • Summary: Foods rich in NAD precursors, like liver and spinach, are high in mitochondria and their coenzymes, which break down into soluble precursors. Measuring blood NAD levels reflects recent precursor intake, but this may not fully represent NAD status in other critical organs.
Disease States Taxing NAD
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(00:16:48)
  • Key Takeaway: NAD systems are significantly taxed in conditions including heart failure, neurodegeneration, obesity, and insulin resistance.
  • Summary: Animal studies show the NAD system is attacked in heart failure and neurodegeneration. Overfeeding mice led to disturbed liver NAD and degraded detoxification capacity due to insulin resistance. Lack of sleep or circadian disruption is also assured to disturb the NAD system.
NR’s Anti-Inflammatory Effects
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(00:20:32)
  • Key Takeaway: Nicotinamide riboside (NR) at gram-a-day doses is a proven anti-inflammatory agent in human randomized controlled trials (RCTs).
  • Summary: NR strongly lowers inflammatory markers like IL-6 and IL-10, an effect so strong it persisted briefly even after stopping supplementation. This anti-inflammatory action is hypothesized to occur by replenishing NAD supplies, allowing better detoxification of free radical species.
Single Biggest Lifestyle Change for NAD
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(00:25:17)
  • Key Takeaway: For common chronic conditions, the most impactful lifestyle change for supporting NAD is addressing the primary driver, such as weight loss for obesity or fixing circadian rhythm disruption.
  • Summary: There is no one-size-fits-all recommendation; interventions must target the specific underlying cause of inflammation and NAD depletion. For overweight individuals, medical options combined with resistance training are now effective strategies for weight loss.
Cognitive Benefits of NAD Precursors
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(00:28:01)
  • Key Takeaway: Oral NAD precursors increase brain NAD, and NR has been shown to improve cerebral blood flow in individuals with mild cognitive impairment.
  • Summary: Imaging experiments confirm oral NAD precursors raise brain NAD levels. A recent study on long COVID patients showed within-group improvements in executive function and mood when taking NR. It is hypothesized that reducing baseline inflammation correlates with improved cognitive outputs.
Value of NAD Blood Testing
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(00:31:37)
  • Key Takeaway: NAD testing is valuable for clinical trials but unnecessary for healthy individuals already taking NR, as supplementation reliably boosts levels.
  • Summary: If taking NR from a reputable source, it is expected to boost NAD within six to eight hours, negating the need for personal testing. Over-testing the ‘worried well’ is discouraged, as it drives unnecessary anxiety without providing actionable insight for healthy people.
Exercise and NAD Synthesis
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(00:34:37)
  • Key Takeaway: Exercise increases the gene expression of NAD biosynthetic enzymes, supporting mitochondrial biogenesis and adaptation.
  • Summary: Clinical evidence shows exercise boosts the expression of genes responsible for NAD synthesis. This adaptation supports mitochondrial biogenesis, which is intrinsically linked to NAD-dependent processes like beta-oxidation. Supplementing with NR alongside exercise may offer synergistic benefits for performance and recovery.
Maternal NR Supplementation Effects
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(00:40:46)
  • Key Takeaway: In mice, NR supplementation during pregnancy led to offspring with better lean mass, faster physical development, and lower fear/anxiety levels.
  • Summary: NR-supplemented mothers produced more milk, transferring higher bulk calories and potentially bioactive compounds to their offspring. The mammary NAD levels were greatly increased in supplemented mothers, suggesting NAD is actively distributed to support lactation.
NR Timing and Circadian Rhythms
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(00:48:37)
  • Key Takeaway: It is logical to take NR in the morning alongside breakfast to align nutrient and coenzyme synthesis with the body’s primary metabolic cycle.
  • Summary: NR does not act as a stimulant, but morning dosing aligns with the body’s natural intake of macronutrients requiring coenzymes for conversion. For shift workers starting their cycle late (e.g., 11 PM), taking NR at the beginning of their work period is the most logical timing.
NAD vs. Precursors Supplementation
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(00:54:20)
  • Key Takeaway: Oral NAD supplements are ineffective because the molecule cannot enter cells; precursors like NR must be taken to boost cellular NAD.
  • Summary: NAD cannot enter cells due to its phosphate groups, and NMN also struggles to enter cells because it already possesses a phosphate group, often converting back to NR extracellularly. NR is the most safety-tested precursor that can enter cells and be phosphorylated into NAD.
NAD IV Drips vs. Oral NR
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(00:58:07)
  • Key Takeaway: Intravenous NAD infusions are painful because NAD cannot enter cells, but clinical-grade intravenous NR is now available and may deliver higher tissue concentrations than oral dosing.
  • Summary: NAD IV drips cause an innate immune response because the molecule cannot cross cell membranes effectively. Oral NR has significantly more extensive clinical data supporting its safety and efficacy than IV delivery currently. IV NR delivery may offer superior biodistribution to specific tissues like the heart.
NMN vs. NR Chemical Logic
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(01:02:37)
  • Key Takeaway: NMN is chemically illogical as an oral supplement because it must be degraded back into NR to enter cells, as its phosphate group prevents cellular uptake.
  • Summary: The phosphate group on NMN prevents its transport into the cell, meaning it is converted back to NR before it can be utilized. NR, being a nucleoside without a phosphate, is readily taken up by cells where it is then converted into NMN and subsequently NAD.
Gut Microbiome Influence on NAD
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(01:05:44)
  • Key Takeaway: NR supplementation positively alters the gut microbiome composition in humans, suggesting a beneficial interaction between the precursor and gut bacteria.
  • Summary: Research indicates that NR supplementation alters the microbiome in a beneficial way, potentially by converting some NR into nicotinic acid for bacterial use. The effects of NR on tissue NAD are observable even when NR itself is difficult to detect in the blood due to rapid uptake and enzymatic breakdown.
NR for Immune Function and Infection
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(01:08:22)
  • Key Takeaway: NR shows promise in immune-related conditions by lowering inflammation and has been shown in combination therapies to reduce the time to recovery from COVID-19.
  • Summary: NR has demonstrated activity in conditions where the inflammosome is activated, supported by eight RCTs showing anti-inflammatory effects. While trials testing NR alone for infection prevention were not conducted during the pandemic, combination therapies showed reduced illness duration.
NR Benefits for Peripheral Artery Disease
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(01:11:41)
  • Key Takeaway: A clinical trial demonstrated that NR supplementation improved the six-minute walk test in patients with peripheral artery disease, while resveratrol blocked this benefit.
  • Summary: Patients with peripheral artery disease often show functional decline over six months, but NR improved their walking distance in a three-arm trial. The addition of resveratrol negated the positive effects of NR, suggesting resveratrol is ineffective or detrimental in this context.
NR and Liver Fat Reduction
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(01:16:05)
  • Key Takeaway: Human clinical trial endpoints regarding NR’s effect on weight loss or insulin sensitization in obese, diabetic populations were often set unreasonably short (e.g., 13 weeks).
  • Summary: The expected benefits of NR on metabolic syndrome markers like weight loss are difficult to observe in short human trials compared to rapid results seen in mouse models. Future research may examine liver tissue from bariatric surgery patients to assess NAD changes related to obesity.
NR Effects on Liver Fat
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(01:15:55)
  • Key Takeaway: A clinical trial showed a substantial, though statistically non-significant, reduction in hepatic fat (10 absolute percent points) in overweight, diabetic men taking NR.
  • Summary: A 2018 trial involving overweight, insulin-resistant Danish men showed NR reduced liver fat from approximately 21% down to 11%. The primary endpoint of weight loss and insulin sensitivity failed, but the liver fat signal was strong (P=.13). Future trials should randomize based on liver fat and incorporate exercise or GLP-1 medication to better observe NR’s effect.
Healthy Individual Supplementation Rationale
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(01:21:29)
  • Key Takeaway: For healthy, active individuals, the best argument for adding an NAD precursor is improving workout recovery and potentially reducing inflammation.
  • Summary: Lifestyle changes like diet and exercise remain the most important factors for health improvement. Adding NR is best justified for athletes or active people seeking an edge in recovery, especially since exercise synergizes well with NAD precursors. The host confirmed personal positive experience with recovery while taking 1000mg of NR daily.
NR Dosing and Safety Limits
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(01:23:00)
  • Key Takeaway: Clinical trials typically use 500mg to 1000mg of NR daily, and while safety testing has gone up to 3 grams per day, exceeding that amount is not recommended.
  • Summary: A reasonable dose for most people appears to be between 500mg and 1000mg of NR. The safety and source of the NR material are crucial considerations. Testing has supported safety up to 3 grams per day in certain populations, but going beyond that is generally advised against without specific medical guidance.
Stacking NR with Resveratrol/Pterostilbene
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(01:24:59)
  • Key Takeaway: Resveratrol and pterostilbene offer no proven use case for boosting NAD and pterostilbene may negatively impact health by dose-dependently increasing LDL cholesterol.
  • Summary: There is no established benefit to mixing NAD precursors with resveratrol or pterostilbene, which were historically thought to activate SIRT1. Pterostilbene has been shown to increase LDL cholesterol, which is generally undesirable. Listeners interested only in boosting NAD should avoid these pairings.
Cancer Risk and NAD Precursors
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(01:28:47)
  • Key Takeaway: Population-level clinical data from Australian trials using nicotinamide shows that boosting NAD status is preventative for cancer, specifically lowering non-melanoma skin cancer risk.
  • Summary: The highest level of evidence (large randomized trials) indicates that NAD boosting does not cause cancer; in fact, nicotinamide supplementation lowered cancer risk in the general population. While some animal studies show accelerated tumor growth when NAD precursors are given to mice with existing tumors, this context is not reflective of human cancer development. Individuals undergoing chemotherapy should consult their doctor regarding supplementation.
Worthwhile Use Cases for NR Supplementation
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(01:34:37)
  • Key Takeaway: NR supplementation is worthwhile not just for age, but for specific high-demand situations like intense workout schedules, recovery for collision athletes, and potentially reducing susceptibility to common infections.
  • Summary: Dr. Brenner affirms that NR has multiple use cases beyond just age, citing 20-year-old football players needing rapid recovery. The compound may also offer benefits in supporting immune function when exposed to pathogens in crowded environments. Future trials are expected to explore use cases in peripheral artery disease, fertility, and fatty liver disease.
Brenner’s Discovery of NR Pathway
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(01:38:56)
  • Key Takeaway: Dr. Brenner’s investigation into the NAD synthetase enzyme, which required glutamine, led him to hypothesize and subsequently test for the existence of the previously unknown Nicotinamide Riboside (NR) pathway for NAD synthesis.
  • Summary: His initial focus was on an enzyme that converts NAAD to NAD, which required glutamine, a requirement that was unexplained in prior literature. By knocking out the gene for this enzyme in yeast, he created a situation where NAD synthesis would fail unless an alternative pathway existed. This led him to set up experiments to confirm the NR pathway, revealing a new route to the central metabolic catalyst.
Three Core Roles of NAD Coenzymes
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(01:48:03)
  • Key Takeaway: NAD coenzymes are critical for the three major metabolic functions: converting fuel into ATP, building necessary cellular components (anabolism), and repairing cellular damage.
  • Summary: NAD+ and NADH handle energy transfer by collecting high-energy electrons from food and passing them down the electron transfer chain to drive ATP synthesis. NADP and NADPH are essential for anabolism, providing high-energy electrons needed to synthesize lipids, nucleic acids (DNA/RNA), and proteins. Furthermore, NADPH is vital for detoxifying reactive oxygen species generated during metabolism.
NAD in DNA Repair and Gene Regulation
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(01:52:41)
  • Key Takeaway: The enzyme PARP1 is a massive consumer of NAD, using it to create poly-ADP ribose polymers that signal and assemble DNA repair machinery at sites of damage.
  • Summary: When DNA damage occurs, PARP1 consumes NAD to modify proteins, signaling the need for repair enzymes. Other NAD-consuming enzymes, like sirtuins, regulate gene expression by removing modifications (like acetyl groups) from protein lysines. If NAD becomes limiting, these critical repair and regulatory functions can be compromised.