#109 How To Boost NAD Levels To Fight Inflammation, Improve Recovery, and Slow Aging | Dr. Charles Brenner
Dr. Charles Brenner, a distinguished biochemist and leading NAD expert, discusses how nicotinamide riboside (NR) effectively boosts NAD levels. He covers NR's anti-inflammatory benefits, its role in conditions like obesity and peripheral artery disease, and practical guidance on supplementation and lifestyle factors for supporting NAD.
Deep Dive Analysis
20 Topic Outline
Introduction to Dr. Charles Brenner and NAD Biology
Re-evaluating NAD Decline with Age and Tissue Specificity
Inflammatory Processes and NAD System Disturbance
Coronavirus Infection and PARP Activation's Impact on NAD
Obesity, Insulin Resistance, and NAD System Stress
Nicotinamide Riboside (NR) as an Anti-Inflammatory Agent
Lifestyle Changes for Optimal NAD Support
Cognitive Benefits of NAD Precursors and Cerebral Blood Flow
The Utility of Measuring NAD Levels
Exercise's Role in Boosting NAD and Recovery
NR Supplementation for Maternal and Offspring Health
Addressing Circadian Rhythm Disruption and Jet Lag with NR
Differentiating NAD Supplements, Precursors, and IV Drips
NMN vs. NR: Understanding Bioavailability and Mechanism
Gut Microbiome's Influence on NAD Metabolism
NR's Therapeutic Potential in Peripheral Artery Disease
NR's Potential for Reducing Liver Fat
Dosing, Stacking, and Sourcing Considerations for NR
Addressing Cancer Risk and NAD Precursors
NAD's Foundational Role in Cellular Energy, Repair, and Gene Regulation
6 Key Concepts
NAD (Nicotinamide Adenine Dinucleotide)
NAD is a central catalyst in metabolism, acting as cellular 'wiring' for high-energy electrons. It collects electrons from food (NAD+) to form NADH, which then distributes them to power ATP synthesis, build molecules (via NADPH), and repair cellular components.
Nicotinamide Riboside (NR)
NR is a potent vitamin precursor to NAD, discovered by Dr. Brenner, that effectively boosts NAD levels in human tissues. It's unique because it can enter cells directly, unlike NMN or NAD itself, and has shown anti-inflammatory benefits in clinical trials.
PARP-1 (Poly-ADP Ribose Polymerase 1)
PARP-1 is an NAD-dependent enzyme that detects DNA damage and consumes NAD to form poly-ADP ribose polymers. These polymers act as a signal to recruit DNA repair enzymes, highlighting NAD's critical role in maintaining genomic integrity.
Sirtuins
Sirtuins are a family of NAD-consuming enzymes that regulate gene expression and cellular processes by removing modifications from proteins, such as acetyl groups from lysines, thereby influencing enzyme activity and gene silencing.
Inflammaging
Inflammaging refers to the chronic, low-grade inflammation that often accompanies aging and contributes to various age-related diseases. This inflammatory state profoundly taxes the NAD system across different tissues, making NAD replenishment a potential strategy to mitigate its effects.
NMN (Nicotinamide Mononucleotide)
NMN is an NAD precursor that, despite being 'one step closer' to NAD in cellular synthesis, must be degraded back to NR to enter cells due to its phosphate group, before being re-phosphorylated to NMN and then NAD inside the cell.
12 Questions Answered
While human blood NAD levels may not universally decline with age, there is strong evidence that NAD pools in specific human tissues are disturbed or decline with age, particularly in the presence of disease and chronic inflammation.
Inflammatory processes, such as those seen in coronavirus infection, obesity, and insulin resistance, activate NAD-consuming enzymes like PARPs, profoundly taxing and disturbing the NAD system in various tissues.
Measuring blood NAD levels may not fully reflect what's happening in other tissues like the brain, muscle, or liver, where significant age-related or disease-driven declines in NAD can occur without being evident in the blood.
Oral NAD precursors have been shown in imaging experiments to increase brain NAD and improve cerebral blood flow in individuals with mild cognitive impairment, suggesting potential functional benefits.
Yes, clinical evidence indicates that exercise leads to an increase in the gene expression of NAD biosynthetic enzymes, contributing to higher NAD levels and supporting mitochondrial biogenesis.
NAD plays a crucial role in cellular repair processes, and supplementing with NAD precursors like nicotinamide riboside is believed to aid in recovery from intense exercise by rebuilding NAD supplies needed for detoxification and repair.
Animal studies show that NR supplementation in pregnant mothers can lead to better lean mass, faster physical development, lower fear and anxiety, and improved adult hippocampal neurogenesis in offspring, partly due to increased milk production and NAD precursor distribution to mammary tissue.
Oral NAD supplements are generally ineffective as NAD itself cannot enter cells; it breaks down into smaller precursors. NAD IV drips are painful and also rely on NAD breaking down into precursors like NR to be utilized by cells, whereas oral nicotinamide riboside is well-tested, not painful, and effectively boosts NAD.
NMN has a phosphate group that prevents its direct transport into cells, requiring it to be degraded back to NR before it can enter and be re-phosphorylated. NR, without the phosphate, can directly enter cells and be converted into NAD.
Recent human studies suggest the gut microbiome plays a role in the conversion of NR and NMN into NAD within tissues, and NR supplementation can positively alter the microbiome.
Clinical trials with nicotinamide (another NAD booster) have shown it lowers the risk of non-melanoma skin cancer, suggesting NAD boosting is not cancer-causing at a population level. However, individuals with existing cancer should consult their doctor.
For healthy, active individuals, a primary benefit of NR supplementation may be improved workout recovery due to its synergistic effects with exercise and its role in reducing inflammation, which can be present even in healthy individuals.
23 Actionable Insights
1. Avoid Universal Fasting Advice
Do not assume that everyone needs to practice fasting or time-restricted feeding, as this advice may be problematic for individuals with disordered eating patterns or those who are already lean.
2. Address Inflammatory Lifestyle Factors
It is necessary to address underlying lifestyle factors that contribute to inflammation, as inflammation profoundly taxes the NAD system across various tissues.
3. Increase Physical Activity
For individuals who are sedentary or spend too many hours in front of a screen, increasing physical activity is likely to be a beneficial step for overall health and NAD support.
4. Exercise to Boost NAD Enzymes
Engage in regular exercise, as it increases the gene expression of NAD biosynthetic enzymes, thereby boosting transcription pathways associated with youth and supporting the NAD system.
5. Address Obesity for NAD Support
If obesity is a driver of chronic inflammation, prioritize weight loss as a high-impact lifestyle change to support the NAD system.
6. Boost NAD, Reduce Inflammation
Consider supplementing with nicotinamide riboside (NR) at doses between 500 to 1,000 milligrams a day to effectively boost NAD levels and leverage its robust clinical evidence for anti-inflammatory benefits.
7. Prioritize Reputable NR Sources
When choosing nicotinamide riboside (NR) supplements, prioritize reputable sources that provide the same clinically tested material, as many products may not contain the advertised ingredients or may have unknown contaminants.
8. Choose Third-Party Tested Supplements
Always choose third-party tested supplement brands, such as those with NSF certification, to ensure they contain the active ingredient as labeled and are free from harmful contaminants, a common issue in the nutraceutical industry.
9. Morning NR for Circadian Alignment
Take nicotinamide riboside (NR) in the morning to align with circadian biology, as this timing is considered important for practical guidance on supplementation.
10. Align NR with Shift Work “Morning”
For shift workers, take nicotinamide riboside (NR) at the beginning of your work cycle (e.g., 10 PM if starting at 11 PM) as this aligns with your “morning” and is considered the most logical timing.
11. Mitigate Jet Lag with Light & Sleep
When traveling internationally, adjust your calendar to the destination’s time, try to sleep when locals are sleeping, and get bright sunlight at 6 or 7 a.m. local time to help reset your circadian rhythm.
12. NR with Morning Light for Jet Lag
Consider taking nicotinamide riboside (NR) in the morning along with bright sunlight to help reset your circadian rhythm when experiencing jet lag or time zone disruption.
13. Consider NR for Workout Recovery
Consider supplementing with nicotinamide riboside (NR) for enhanced workout recovery, especially for those engaged in intense physical activity or collision sports, as it synergizes well with exercise.
14. Consider NR for Immune Support
Consider supplementing with nicotinamide riboside (NR) to potentially reduce the frequency of getting sick, especially if you are often in crowded environments where infections like the flu or COVID are prevalent.
15. Consider NR for Fertility
Women trying to conceive may consider supplementing with 500 milligrams to a gram of nicotinamide riboside (NR) daily, as animal studies show strong results for fertility and developmental outcomes, and some fertility doctors recommend it.
16. NR for Improved Maternal Lactation
New mothers may consider supplementing with nicotinamide riboside (NR) to potentially improve maternal lactation and produce more milk, which can lead to better weight management and developmental outcomes in offspring.
17. Prioritize Oral NR Over IV NAD
Opt for oral nicotinamide riboside (NR) supplementation over intravenous NAD therapies, as oral NR has much more extensive clinical data supporting its safety and efficacy, while NAD itself cannot easily enter cells.
18. Choose NR Over NMN Supplementation
When considering NAD precursors, prefer nicotinamide riboside (NR) over nicotinamide mononucleotide (NMN), as NMN must break down into NR to enter cells due to its phosphate group.
19. Choose Safety-Tested NR
Select nicotinamide riboside (NR) as your NAD booster due to it being the most safety-tested option on the market, offering a reliable choice for supplementation.
20. Limit NR Dose to 3 Grams
For most people, a substantive dose of nicotinamide riboside (NR) is 500 to 1,000 milligrams, and while it has been safety tested up to 3 grams per day in certain populations, it is not recommended to exceed this upper limit.
21. Avoid Resveratrol & Terastilbene
Avoid supplementing with resveratrol and terastilbene, as there is no evidence basis for their efficacy as SIRT1 activators, and terastilbene may increase LDL cholesterol.
22. Avoid Resveratrol with NR
Do not combine nicotinamide riboside (NR) with resveratrol, as resveratrol was shown to block some of the beneficial effects of NR supplementation in clinical trials.
23. Consult Doctor for Cancer & NR
If you have cancer or are undergoing chemotherapy, consult your doctor before taking NAD precursors like nicotinamide riboside (NR), as it could potentially be contraindicated in specific situations.
5 Key Quotes
When people say NAD levels decline in age, 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. But I think that the idea that every human system's NAD declines in age is probably overstated.
Dr. Charles Brenner
The exercise that you do is infinitely better than the exercise that you plan to do or wish you did.
Dr. Charles Brenner
The thing that your listeners need to know, or watchers need to know, is that high energy electrons run us as well. They run living things as well. And the wiring for the high energy electrons are basically NAD coenzymes.
Dr. Charles Brenner
The way living things work is they couple all of the energy transfers to reactions that need to be run. And we don't let the high energy electrons go up in smoke.
Dr. Charles Brenner
In a big organism like us with 37 trillion cells or however many we have, it's better for us to lose some cells than to try to repair everything.
Dr. Charles Brenner
2 Protocols
Mitigating Circadian Disruption with NR (Speculative)
Dr. Charles Brenner- Set your calendar to the destination time zone.
- Try to sleep when people in the destination time zone are sleeping.
- Get bright sunlight at 6 or 7 AM in the destination time zone.
- Consider taking nicotinamide riboside (Niagen) in the morning of the new time zone.
- Engage in activity to help reset your body.
General NAD Boosting Strategy (Implied)
Dr. Charles Brenner- Address underlying lifestyle factors causing chronic inflammation (e.g., obesity, alcohol, sedentary lifestyle, chronic sleep deprivation).
- Engage in regular exercise (any type is better than none).
- Consider supplementing with nicotinamide riboside (NR) at 500-1000 mg/day, ideally in the morning.