Boosting NAD+: Strategies for a Healthier Lifespan

NAD+ (Nicotinamide Adenine Dinucleotide) is a critical coenzyme in every cell, supporting numerous biological processes. Here are the key benefits of maintaining healthy NAD+ levels:

• Energy Production: NAD+ is essential for cellular metabolism, facilitating the conversion of nutrients into ATP, the cell's primary energy source, through processes like glycolysis, the citric acid cycle, and oxidative phosphorylation.
• DNA Repair: NAD+ activates enzymes like PARP-1, which repair DNA damage caused by oxidative stress or aging. This helps maintain genomic stability, reducing the risk of mutations and age-related diseases.
• Cellular Defense and Longevity: NAD+ supports sirtuins, proteins that regulate cellular health, stress resistance, and lifespan. Sirtuins promote anti-aging effects by enhancing DNA repair, reducing inflammation, and improving metabolic efficiency.
• Improved Mitochondrial Function: NAD+ enhances mitochondrial health, ensuring efficient energy production and reducing oxidative stress, which is linked to aging and chronic diseases.
• Neuroprotection: NAD+ supports brain health by protecting neurons from oxidative damage and inflammation, potentially reducing the risk of neurodegenerative diseases like Alzheimer’s and Parkinson’s.
• Cardiovascular Health: NAD+ promotes blood vessel function and heart health by supporting sirtuins and reducing oxidative stress, potentially lowering the risk of cardiovascular diseases.
• Metabolic Health: NAD+ regulates insulin sensitivity, glucose metabolism, and fat storage, helping prevent obesity, type 2 diabetes, and metabolic syndrome.
• Reduced Inflammation: NAD+ modulates immune responses and inhibits enzymes like CD38, which are linked to chronic inflammation ("inflammaging"), a driver of age-related decline.
• Enhanced Muscle Function: NAD+ supports muscle repair and maintenance by improving mitochondrial function and reducing oxidative damage, aiding physical performance and recovery.
• Cognitive and Physical Resilience: Higher NAD+ levels are associated with improved cognitive function, memory, and physical endurance, supporting overall vitality during aging.

Maintaining NAD+ levels through diet (e.g., flavonoid-rich foods), lifestyle (e.g., calorie restriction), or supplements (e.g., nicotinamide riboside) may enhance these benefits, potentially improving healthspan and lifespan. However, consult a healthcare professional before making changes to boost NAD+.

The Third Way to Boost NAD+ (YouTube link)

In the video, it discusses three strategies to boost NAD+ levels, which are crucial for cellular health and longevity:

• Increasing NAD+ Precursors: Supplying more precursors to produce NAD+.
• Enhancing NAD+ Synthesis: Activating enzymes that synthesize NAD+ to increase production.
• Reducing NAD+ Consumption: Conserving NAD+ by minimizing its use by enzymes like PARP-1 and CD38.

PARP-1 is an enzyme that consumes NAD+ to repair DNA damage. Excessive oxidative stress, such as from a high-fat diet, increases DNA damage, activating PARP-1 and depleting NAD+. This can be mitigated by reducing oxidative stress through diet, like consuming purple sweet potatoes rich in anthocyanin pigments, which restore NAD+ levels. While PARP-1 blockers could preserve NAD+, preventing DNA damage is preferable. Higher PARP-1 activity correlates with longer lifespans, but overactivation can deplete NAD+ and cause cell death.

CD38, another NAD+ consumer, is linked to inflammation and increases with age due to "inflammaging." Blocking CD38 in old mice restores NAD+ to youthful levels. Conditions like obesity, characterized by oxidative stress and inflammation, reduce protective sirtuin activity, which relies on NAD+. Calorie or protein restriction can boost sirtuin expression and NAD+ levels by reducing oxidative stress.

Dietary Interventions: Antioxidant and anti-inflammatory flavonoids in plant foods inhibit PARP-1 and CD38, boosting NAD+ and sirtuin activity. 

Effective compounds include:

• Cyanidin (red cabbage, blackberries)
• Quercetagetin (marigold tea)
• Luteolin (oregano, radicchio, chrysanthemum tea)
• Kuromanin (blackberries, purple corn, hibiscus tea)
• Luteolinidin (red sorghum)
• Apigenin (parsley, chamomile tea)
• Proanthocyanidins (apples, plums, wild blueberries, cinnamon, cocoa powder)
• Quercetin (onions)

These compounds, found in fruits, vegetables, and spices, can achieve NAD+-boosting effects at dietary levels. For example, one apple or two plums provide enough proanthocyanidins to lower PARP-1 and CD38 expression, while two onions can raise quercetin levels sufficiently. High-dose flavonoid supplements lack long-term safety data, so a balanced vegetarian diet is recommended to safely increase NAD+ levels.

Dr. Greger's Plant-Based Prescription for Health and Longevity

Nutrition Expert: These are The Best Foods to Eat to Live Longer | Dr. Michael Greger (YouTube link)

Dr. Michael Greger, a renowned advocate for evidence-based nutrition, emphasizes the critical role of diet in health and longevity, highlighting that poor diet is the leading cause of death globally, surpassing smoking. He argues that most chronic diseases, including heart disease (evident in nearly all Americans by age 10), stem from "diseases of excess" — too much sodium, saturated fat, and sugar. A plant-based diet, centered on whole, unprocessed plant foods like fruits, vegetables, legumes, whole grains, nuts, seeds, and spices, is the healthiest approach to prevent and even reverse these conditions.

Key Points:

• Diet as the Top Risk Factor: The Global Burden of Disease study identifies diet as the number one killer, with the American diet causing more deaths than smoking. Heart disease, the leading cause of death, is preventable through dietary changes.
• Plant-Based Diet Defined: A plant-based diet prioritizes whole plant foods, minimizing meat, dairy, eggs, salt, and sugar. It’s not necessarily vegetarian but focuses on maximizing healthy choices, avoiding processed foods like soda or chips, which can technically be plant-based but are unhealthy.
• Health Benefits: Centering diets around whole plant foods reduces the risk of chronic diseases, improves energy, digestion, and quality of life, and can extend lifespan. For example, switching to a healthier diet at age 20 can add 11–13 years to life, and even at age 80, it can add 3 years.
• Actionable Swaps: Nutrition is about "instead of what." Replace unhealthy foods with healthier alternatives (e.g., water instead of soda, oatmeal instead of eggs if comparing health impacts). Dr. Greger’s Daily Dozen app recommends incorporating specific healthy foods like berries, dark leafy greens, legumes, and spices daily.
• Top Foods to Add: 
• Berries (healthiest fruits)
• Dark green leafy and cruciferous vegetables (e.g., kale, collards)
• Legumes (beans, chickpeas, lentils) as primary protein sources in Blue Zones.
• Top Foods to Remove: 
• Trans fats (hydrogenated oils)
• Processed meats (bacon, hot dogs, classified as Class 1 carcinogens)
• Sugary beverages (soda).
• Taste Bud Reset: A plant-based diet can recalibrate taste buds in about three weeks, making healthy foods like unsalted corn or sweet potatoes taste delicious as the palate adjusts away from hyper-salty, sweet, or fatty processed foods.
• Supplements Caution: The supplement industry is poorly regulated, with many products not containing what’s claimed or being contaminated. Choose USP-certified brands or whole food sources (e.g., turmeric spice over curcumin pills). Supplements like B12 (for plant-based eaters), vitamin D (for low sun exposure), and algae-based DHA (for cognitive health) may be necessary in specific cases, but most people should focus on diet over pills.
• Behavioral Change: Small, incremental dietary changes compound over time. A two-week plant-based trial can yield noticeable improvements in energy and digestion, encouraging long-term adherence. The goal is to make healthy eating enjoyable, not restrictive, by “loving the food that loves you back.”

Takeaways for Listeners:

• Try Plant-Based for Two Weeks: Expect better energy, digestion, and a recalibrated palate that enjoys whole foods.
• Focus on Whole Plant Foods: Prioritize berries, greens, and legumes while cutting trans fats, processed meats, and soda.
• Start Small, Think Long-Term: Small dietary changes compound to improve health and longevity, and it’s never too late to start.