November 4, 2023

Time and time again, I'm reminded that it's the microscopic intricacies of my body (and yours!) that have monumental effects on my performance, longevity, and well-being.

And Nicotinamide Adenine Dinucleotide (NAD+) status is one of the “biggest” smallest molecules to consider. NAD+ is a molecule of paramount necessity to mitochondrial function, energy production, and yes, aging. Your NAD+ status is one of the most important things to consider not only for your longevity but for your energy and well-being.

Because NAD+ is at the forefront of the health and wellness industry right now, and because I've gotten so many questions about it, I recently published a comprehensive article titled “Everything You Need To Know About NAD+: The Crucial Role It Plays In Your Mitochondrial Health, How NAD+ Slows Down Aging & Increases Energy, Ways To Increase NAD+ Using Lifestyle, Why NAD+ Precursors May Be Problematic & A Safe, Cost-Effective Oral NAD+ Supplement Strategy.” Today, I'm following up on that article with a complementary podcast that's sure to help bolster your understanding of this little miracle molecule.

My first guest on today's show, Dr. Michael Roberts, is a Professor in the School of Kinesiology at Auburn University where he serves as the Director of the Molecular and Applied Sciences Laboratory as well as the Director of the Applied Physiology Laboratory.  Dr. Michael’s laboratory utilizes cell culture, rodent, and basic as well as applied human models to examine how nutrition and/or exercise affects cellular biomarkers and whole-body physiology.  He currently has over 180 publications in several preeminent physiology and nutrition journals, serves in senior editor roles for various physiology journals, and has given numerous lectures at regional, national, and international scientific conferences and venues.

Between the years 2013-2022, Dr. Michael performed contracted research with several industry entities, including (but not limited to): Nutrabolt, The Peanut Institute, Metabolic Technologies, University of Mary Hardin-Baylor, Florida A&M University, the Edward Via College of Osteopathic Medicine, Ritual, Impedimed, Auburn University’s Intramural Grant Program, Future Ceuticals, Chemi Nutra, Center for Applied Health Sciences (CAHS), Applied Sports Performance Institute, Dolcas, MusclePharm, and Axiom Foods.

During this time, Dr. Michael's lab has received gift funds or product donations completely allocated towards research from several industry entities including (but not limited to): Nutrabolt, Maximum Human Performance, Dymatize, Renaissance Periodization, Lockwood LLC, Hilmar Ingredients, BioNutritional Research Group, Future Ceuticals, the Edward Via College of Osteopathic Medicine, and 4Life. Dr. Michael has consulted with JUVN3 Holdings, Compound Solutions and the International Protein Board, and is also a scientific advisor for the International Protein Board.

My other guest, Matt Titlow, is CEO of Compound Solutions, a company that supplies unique, science-backed ingredients to forward-thinking nutrition companies, including Biostack Labs, which we discuss in this podcast – along with the fantastic formula for NAD3 called “Cell Regen” by Biostack Labs. Matt has been in the nutraceutical industry since 2002. He became Compound Solutions’ CEO in 2011, and since then, he has spearheaded the company’s vision to maximize human potential. His vision manifests itself by finding, researching, and representing ingredients from around the world that are backed by science and lead to improved cognitive and physical performance.

Together, Dr. Michael, Matt, and I are diving deep into the world of NAD+. Discover the essential role it plays at the cellular level, the factors that deplete it, and the smorgasbord of ways to naturally elevate its levels. We'll also shed light on groundbreaking research, decode alternative delivery methods, and unveil the truth behind the NAD+ hype. Step with the three of us into the intriguing realm of NAD+, where we'll explore together how this tiny molecule plays an outsized role in your health and vitality.

During our discussion, you'll discover:

-What is NAD+, and what does it do on a cellular level?…08:12

• NAD as an electron carrier
• NAD+ is a kind of energy transfer molecule
• Many new kinds of research in the 2000s
  • Showed that if you elicit nutrient deprivation, you can increase longevity
  • Started to be linked to NAD+ levels increase
• NAD+ vs. NADH
  • NADH is a reduced form that carries electrons
  • NAD+ does not carry electrons
• Podcast with Dr. David Sinclair:
  • Ben Greenfield Interviews Dr. David Sinclair About Lifespan: Why We Age―and Why We Don’t Have To.
• New research showed that NAD+ is
  • Linked to sirtuin activation
  • Mitochondrial NAD levels are linked to cell survival mitochondrial function
  • Certain DNA repair enzymes PARPs are activated by NAD+
• What is PARP?
  • Poly-ATP Ribose Polymerase – aids in repairing damaged DNA
• Even if it’s not an electron carrier, even if it's not helping cell produce ATP, NAD+ has repair and maintenance functions

-How did NAD become so popular?…13:11

• There are several milestone publications about NAD+
• Muscle biopsy and tissue levels of NAD+
  • With aging, NAD+ levels decrease
• MRI imaging of the brain
  • Researchers showed that brain levels showed an incremental decrease of NAD+ with aging
• With skin cells, there's also this linear decrease of NAD+ with aging
• People want to increase their NAD+ levels

-What affects NAD+ levels?…16:11

• Ben's recent article about NAD+:
  • Everything You Need To Know About NAD+: The Crucial Role It Plays In Your Mitochondrial Health, How NAD+ Slows Down Aging & Increases Energy, Ways To Increase NAD+ Using Lifestyle, Why NAD+ Precursors May Be Problematic & A Safe, Cost-Effective Oral NAD+ Supplement Strategy.
• It is not the low levels of vitamin B3 present in old people
• A study on young vs old (60 years plus)
  • Old people had 60% lower levels of NAD
  • Then had them engaged in 10 weeks of resistance training
  • The level of NAD increased to youth levels
• Exercise increased the levels of NAMTP
  • Enzyme responsible for generating and maintaining NAD+ levels
• Cardio vs. Weight training as natural method to increase NAD+ levels
  • Endurance training elevates muscle NAMTP levels
• The role of myostatin
  • Myostatin does not have any link with NAD+
• Immune cells have a protein that's called CD38
  • CD38 is a consumer of NAD+, like PARPs and sirtuins
  • Aging and poor lifestyle decrease NAD+ levels
• Inflammation can be helped out by restoration of NAD+ levels
• It's not about boosting, it's about NAD+ pools
• It's about playing offense and defense
  • You want to reduce the degradation
  • Laying the foundation for a boost
• NAD+ status needs to remain balanced
• It’s not enough to take vitamin B3 to increase NAD+
• Why isn’t taking vitamin B3 enough to boost NAD+ levels?
  • Vitamin B3 or Niacin can boost NAD+ levels
  • Aging is more than just boosting NAD+
• The body is a complex system needs to prevent degradation

-Ways to naturally increase NAD+…32:17

• The big one is exercise
• High blood alcohol levels will lower liver levels of NAD+
• The relationship between DNA+ and sleep deprivation is not clear enough
• Ben’s recipe for sleep deprivation 
  • NAD+ (spend $100 or more and get 15% off)
  • Creatine
• Research shows creatine is good for the brain

-Is there a difference between NAD, NR, and NMN supplements…37:39

• Recent small Japanese research shows there is no difference
• But long-term studies need to be done
• Podcast with Tony Robbins and Peter Diamandis
  • Tony Robbins, Peter Diamandis & Ben Greenfield Reveal New Anti-Aging Biohacks & Breakthroughs in Precision Medicine You’ve Never Heard Of Before.
• Matt partnered with Dr. Tim Ziegenfuss
• What is NAD3?
  • NAD3 is regulating the NAMPT enzyme, which allows the conversion of something like niacinamide into NAD+
• NAD3 in NAD Regen is made of 3 ingredients:
  • Theacrine
  • Wasabi extract
  • Copper (I)- Cuprous Niacin
• The other ingredients:
  • Niacinamide
  • Resveratrol
  • Spermidine
  • Black pepper extract
• The function of the ingredients
  • Anti-inflammatory action
  • Liver function
  • Lipid metabolism
  • Healthy aging – addressing multiple hallmarks of aging
• Podcast with Dr. Dan Pompa:
  • Beyond Fasting: How To Biohack Your Fast To Accelerate Fat Loss, Stave Off Carbohydrate Cravings & Enhance Cellular Autophagy.
• A Systems-Approach to NAD+ Restoration – a study by Nichola Conlon

-Can you have too much NAD+?…45:10

• A systems approach to NAD+ restoration study
• If you have excess inflammation, too much NAD could be bad for you
  • Also, if you have poor methylation status
• Supplements can enhance, but cannot cure
• It’s important to change your lifestyle and establish a baseline before taking supplements
• If you have some genetic methylation issues, you must address them before taking NAD
  • Getting really good bioavailable folate
• Exercise can vastly and robustly affect muscle DNA methylation
  • Exercise should always be first
• You can overdo NAD
• A study with placebo and NAD3 group
  • There was less hyper-methylation of the DNA in the immune cells
  • Less hypo-methylation relative to the control group
• Transcriptomics technique
  • You can look at all of the messenger RNAs that are being expressed in the cells
• Reduction of endoplasmic reticulum stress
  • If it becomes dysfunctional with aging it can cause cellular apoptosis and cell damage
• Aging researchers say one of the reasons why cells may age is that we have a variant and uncontrolled mRNA transcription
• Can the body get used to NAD supplementation?
  • No data on feedback loops
• When taking more than 1g per day, you can have side effects, so over-consuming is not a good idea
• In terms of these defensive mechanisms, there is not enough data

-Alternative ways of NAD delivery…57:29

• Alternative deliveries:
  • NAD IV
  • NAD patches (use code BEN to save $100 off your first order)
  • Suppositories
• It feels over-engineered
• IV may be good if there is gastric distress with larger doses
• NAD+ can't be orally ingested; it's not going to be bioavailable
  • It's not going to just diffuse across the cell membrane
  • That's why you take the precursors
• Creatine monohydrate works
  • How can it be improved?
  • There is no need to improve
• Pharmaceutical companies and their interests

-Circadian rhythm and NAD…1:03:24

• When and how best to take NAD+ (spend $100 or more and get 15% off)
• Theacrine is a dopamine agonist like caffeine
  • It can be a little bit overstimulating
• 12-week study
  • Probably best to take it in the morning
  • Taken with breakfast
• Ben’s experience with NAD IV

-New research on NAD+…1:06:56

• Doing in vitro study on human liver cells with NAD3 (spend $100 or more and get 15% off)
• Compound Solutions
• Living to 120 is Becoming An Imaginable Prospect – The Economist article
• 12 Pillars of Aging
• Dysbiosis as 12th pillar of aging
• Podcast with Colleen Cutcliffe:
  • The New Probiotic Strain That Allows You To Eat Carbs Again, How GLP-1 Peptide Actually Works And Why It’s Not Intended For Everyone, With Pendulum’s Colleen Cutcliffe.
• Podcast episode with Dr. Sandra Kaufmann:
  • The 7 Different Reasons You Age (& Potent, Proven Molecules To Enhance Longevity & Slow Aging).
• The Kaufmann Protocol: Why We Age and How to Stop It by Dr. Sandra Kaufmann
• The plan is to keep studying NAD3, but also look for different combinations

Upcoming Events:

• Elements of Vitality: December 8th, 2023

Return to the Elements of Vitality—this will be the second time my good friend Dr. John Lieurance and I collaborate to bring you the most effective and cutting-edge health and wellness advice, protocols, and some of our favorite tools. If you’re into health and wellness, and you want to stay on top of all of the cutting-edge, latest, and greatest innovations and protocols, you don’t want to miss this event. Learn more here and use code GREENFIELD for 5% off at checkout.

• Keep up on Ben's LIVE appearances by following bengreenfieldfitness.com/calendar!

Click here for the full written transcript of this podcast episode.

Resources from this episode:

– Dr. Michael Roberts and Matt Titlow:

• • • Molecular and Applied Sciences Laboratory
    • Compound Solutions
    • Biostack Labs (spend $100 or more and get 15% off)

– Podcasts And Articles:

• • • Ben Greenfield Interviews Dr. David Sinclair About Lifespan: Why We Age―and Why We Don’t Have To.
    • Everything You Need To Know About NAD+: The Crucial Role It Plays In Your Mitochondrial Health, How NAD+ Slows Down Aging & Increases Energy, Ways To Increase NAD+ Using Lifestyle, Why NAD+ Precursors May Be Problematic & A Safe, Cost-Effective Oral NAD+ Supplement Strategy.
    • Tony Robbins, Peter Diamandis & Ben Greenfield Reveal New Anti-Aging Biohacks & Breakthroughs in Precision Medicine You’ve Never Heard Of Before.
    • Beyond Fasting: How To Biohack Your Fast To Accelerate Fat Loss, Stave Off Carbohydrate Cravings & Enhance Cellular Autophagy.
    • The New Probiotic Strain That Allows You To Eat Carbs Again, How GLP-1 Peptide Actually Works And Why It’s Not Intended For Everyone, With Pendulum’s Colleen Cutcliffe.
    • The 7 Different Reasons You Age (& Potent, Proven Molecules To Enhance Longevity & Slow Aging).

– Books:

• • • The Kaufmann Protocol: Why We Age and How to Stop It by Dr. Sandra Kaufmann

– Other Resources:

• • • Vitamin B3
    • Kion Creatine
    • Niacin
    • NAD IV
    • NAD patches (use code BEN to save $100 off your first order)
    • NAD Suppositories
    • Dr. Tim Ziegenfuss
    • A Systems-Approach to NAD+ Restoration – A Study by Nichola Conlon
    • The Effects of a Multi-Ingredient Supplement Containing Wasabia Japonica Extract, Theacrine, and Copper (I) Niacin Chelate on Peripheral Blood Mononuclear Cell DNA Methylation, Transcriptomics, and Sirtuin Activity
    • Enhance Trial: Effects of NAD3® on Hallmarks of Aging and Clinical Endpoints of Health in Middle Aged Adults: A Subset Analysis Focused on Blood Cell NAD+ Concentrations and Lipid Metabolism

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Do you have questions, thoughts, or feedback for Matt Titlow, Michael Roberts, or me? Leave your comments below, and one of us will reply!