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.