Summary
Jim Kwik hosts Dr. Andrew Salzman, a Harvard-trained physician and Chief Medical Officer at Wonderfeel, for a deep conversation about NAD's central role in cellular energy, brain performance, and aging. Dr. Salzman explains that NAD is involved in over 500 reactions in the body and that by age 50, most people have lost roughly half their NAD levels compared to their 20s. He uses the bathtub analogy: NAD levels depend on both production (the spigot) and depletion (the drain), and with aging the drain gets bigger primarily due to the inflammatory enzyme CD38. The episode focuses heavily on NAD's importance for brain function, noting that the brain receives 25% of cardiac output despite being a relatively small organ. Dr. Salzman shares anecdotal evidence of cognitive improvement in elderly patients, including a woman who resumed doing crossword puzzles after years of decline. They discuss NMN as a precursor that can be taken orally to boost NAD, with a recommended dose of 900 milligrams daily, and typical results appearing within 4-6 weeks. Salzman argues that aging is not purely passive and that maintaining NAD levels through supplementation, combined with exercise, diet, and mental health, can meaningfully slow the decline.
Key Points
- NAD is involved in more than 500 reactions in the body and is central to energy production, immune response, blood pressure regulation, and brain function
- By age 50, NAD levels drop approximately 50% compared to levels in your 20s
- The bathtub analogy: NAD levels depend on production (spigot) and depletion (drain); aging primarily enlarges the drain through CD38 enzyme activity
- The brain receives 25% of all cardiac blood flow, making it the most energy-intensive organ and highly sensitive to NAD depletion
- NMN is a natural precursor to NAD that can be taken orally, absorbed through the digestive tract, and converted to NAD inside cells
- CD38, an inflammatory enzyme, is the primary cause of NAD depletion with aging; it directly cleaves NAD molecules
- Recommended NMN dose is 900 mg daily, with noticeable results typically appearing within 4-6 weeks
- Reducing inflammation through exercise, good diet, and healthy lifestyle helps preserve NAD by keeping CD38 levels lower
Key Moments
NAD controls over 500 reactions and is the maestro of biology
Dr. Salzman explains that NAD is involved in more than 500 reactions in the body and uses the bathtub analogy to describe how NAD levels depend on both production and depletion, with levels falling roughly 50% by age 50.
"NAD as a molecule is involved in more than 500 reactions in our body. It is a key maestro, if you will, of this entire process."
The brain is the most energy-consuming organ
Dr. Salzman explains that the brain receives 25% of all cardiac blood flow and is the most energy-intensive organ in the body, making it particularly vulnerable to NAD depletion and associated cognitive decline.
"The brain is actually not a big organ in our body, but surprisingly, it receives 25% of all of the blood flow from the heart."
NMN dosing and timeline for results
Dr. Salzman recommends 900 milligrams of NMN daily, taken in the morning, with noticeable results typically appearing within 4-6 weeks. Studies up to 2500 mg showed no adverse side effects.
"We recommend 900 milligrams."
CD38 inflammation drives NAD depletion with aging
Dr. Salzman explains that staying healthy and free of inflammation is the number one way to avoid NAD depletion, because inflammation drives production of CD38, an enzyme that cleaves NAD in half.
"Certainly, staying healthy and free of inflammation is the number one way to avoid depletion of NAD."
