Discover the Science and Benefits of NAD+

Why are some people light on their feet and mentally spry well into their 80s and 90s while others have difficulty decades sooner? In the quest to learn more, scientists have uncovered interesting information about NAD+, a building block of cellular health, longevity, and wellness.

What is NAD+?

When we think of aging, we don’t typically think of our biological age, our age at the cellular level. NAD+ is a coenzyme, a critical component necessary for cellular function, metabolic health, and energy.

NAD+ stands for nicotinamide adenine dinucleotide, a coenzyme that supports the energy production required by a cell’s powerhouse, the mitochondria. The NAD+ cell regenerator also repairs DNA and communicates between cells.

NAD+ is comprised of two forms of vitamin B3, nicotinamide and nicotinic acid, synthesized in the body. It is responsible for chemical reactions required for cellular metabolism and many pathways of cellular communication. 

NAD+ and Its Role in Driving ATP Production

Simply put, the primary function of NAD+ is to transfer electrons between molecules of the cell to drive production of ATP, or adenosine triphosphate, the central energy currency of cells.

ATP is made of three components:

• Adenine, a nitrogenous base
• Ribose, a sugar
• Three phosphate groups, which create the chemical bonds where the energy in ATP is stored.

When hydrolysis breaks these bonds, ATP’s energy is released and the mitochondria uses it to power different cellular processes, such as metabolic reactions, transporting substances across cell membranes, muscle contractions, nerve impulses, or chemical synthesis.

NAD+ supports ATP production through several metabolic pathways:

1. Glycolysis – In the first stage of cellular respiration, NAD+ accepts electrons in the glycolysis process, where it is reduced to NADH, which then ferries electrons to the electron transport chain.
2. Tricarboxylic Acid (TCA) Cycle – Within the mitochondria, NAD+ accepts electrons and is also reduced to NADH.
3. Electron Transport chain and Oxidative Phosphorylation – NADH produced in the earlier steps then donates electrons to the electron transport chain. This process creates a proton gradient that pushes ATP synthesis through ATP synthase.

NAD+ levels as well as the NAD+/NADH ratio influence many aspects of cellular metabolism. They are linked to:

• Membrane phospholipid metabolism and overall energy levels
• The impact of energy production as related to aging

The vital role NAD+ plays in ATP production is an intricate relationship played out at the cellular level to support the delicate balance of metabolic function.

NAD+ Function Beyond Energy Production

There are functions of NAD+ for life extension beyond facilitating and balancing ATP production. These include:

DNA Repair

NAD+ acts as a substrate for poly(ADP-ribose) polymerases (PARPs), particularly PARP1, PARP2, and PARP3, which detect and repair DNA damage. As such, depleted NAD+ levels can reduce DNA repair capacity, and supplementing NAD+ demonstrates the ability to positively impact DNA repair.

 Oxidative Stress Response

In managing oxidative stress, NAD+ helps maintain the cellular redox balance crucial for protecting cells against oxidative damage, which contributes to cellular aging. NAD+ also regulates antioxidant defense mechanisms, helping cells cope with oxidative challenges.

Sirtuin Activation

Sirtuins are a family of proteins with diverse cellular functions, including mitochondrial biogenesis, cellular stress resistance, inflammatory responses, circadian rhythm regulation, and aging processes. NAD+ is a co-substrate that activates sirtuin function. Not only does it help sirtuins with these functions, it also helps regulate gene expression and cellular homeostasis for NAD+ life extension.

The discovery that NAD+ is what activates sirtuins was a crucial finding in the 1990s, which gave scientists clues with how sirtuins link with the metabolic process. Researchers began learning how cross-communication with biological functions were related, i.e., that metabolism was part of a greater form of health and wellness. NAD+ and sirtuin function has become the focus of more research as a result.

The Effects of NAD+ Decline

As with many cellular building blocks, NAD+ levels decrease with age. Given its role in so many cellular processes, the decline of NAD+ levels may contribute to age-related diseases and conditions.

Lower NAD+ levels contribute to aging and decline in the following ways:

• Impaired mitochondrial function, leading to decreased energy production and accelerated cellular aging.
• Accumulated DNA damage, particularly of the skin, due to lowered DNA repair mechanisms due to fewer PARPs in play.
• Reduced activity from sirtuins, particularly SIRT1 which is key for metabolic regulation, leading to a decline in cellular metabolism, which increases metabolic disorders such as insulin resistance and diabetes.
• Increased or chronic inflammation due to lower NAD+ levels associated with specific inflammation markers, and leads to “inflammaging,” contributing to various age-related conditions.
• Neurodegenerative processes from reduced NAD+ in the nervous system contribute to the progression of diseases like Alzheimer’s, Parkinson’s, ALS, and the effects on axon health, contributing to increased neuronal death.
• Stem cell exhaustion occurs with lower NAD+ levels, including muscle stem cells, contributing to lower tissue regeneration capacity with age.
• Reduced sirtuin activity due to lowered NAD+ levels affects gene expression patterns. This contributes to age-related changes in gene expression.
• Cardiovascular health is affected when NAD+ decline contributes to endothelial dysfunction and reduces vascular health, which raises the risk of cardiovascular disease.

NAD+ levels have a far-reaching capacity to reflect how sharply we age and how our cells respond to age-related conditions. The scientific community is studying the preservation and restoration of NAD+ levels to improve health and longevity.

Benefits of NAD+

As our understanding of the effects of NAD+ on the body and its cells grows, we are learning how supplementing NAD+ levels can provide many key benefits, including:

1. Anti-aging and longevity through sirtuin activation and cellular repair and regeneration.
2. Cognitive enhancement and improved mental clarity, focus, and concentration, especially for those experiencing brain fog or managing cognitive decline. NAD+ has been shown to protect against neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and dementia.
3. Improved energy levels by supporting mitochondrial function, ATP production, and combating fatigue. Individuals with chronic fatigue or seeking to recover from illness or chronic conditions may use NAD+ therapy to restore energy.
4. Addiction recovery by helping reduce cravings, alleviating withdrawal symptoms, and repairing brain cells damaged by substance abuse.
5. Improved athletic performance and recovery through enhanced endurance and stamina as well as optimizing cellular energy production.
6. Metabolic balance and weight loss due to NAD+ therapy regulating metabolic processes, improving insulin sensitivity, managing blood sugar, and reducing the risk of metabolic diseases like Type 2 Diabetes and metabolic related disorders.
7. Mood stabilization and mental health treatment with NAD+ neurotransmitter production. Depression, anxiety, and mood disorder sufferers may see stabilization in emotional states with NAD+ therapy.
8. Mitochondrial health to improve cellular energy production and reduce oxidative stress, which improves overall longevity and wellness.

Can I Increase My NAD+ Levels?

Since NAD+ is naturally occurring, it’s logical to consider whether we can potentially increase the levels in our systems.

Humans get NAD+ from the amino acid precursor nicotinamide riboside (NR), which is thought by scientists to be the best precursor available to NAD+. It’s followed closely by nicotinamide mononucleotide (NMN).

How can we increase NAD+ levels? The quick answer is supplements. Studies into diet, exercise, calorie restriction, and intermittent fasting have shown marginal increases in NAD+ levels. A diet rich in vitamin B3 can help.

But for people seeking sustainably improved NAD+ levels, supplements like EllieMD’s injectable NAD+ and nasal spray are really the most effective way of increasing NAD+ levels reliably.

Are There Side Effects to Supplementing NAD+?

Supplementing NAD+ is typically considered safe and is tolerated well by most patients. There are reports of mild side effects. Consulting with your healthcare provider before starting any supplementation program is always recommended for optimal health outcomes. 

Potential side effects include gastrointestinal discomfort such as stomach upset, nausea, or diarrhea. Vitamin B3 is also known to cause temporary skin redness and warmth known as skin flushing. NAD+ supplements may also interact with certain medications, such as blood thinners or blood pressure prescriptions. Always consult with your physician before combining supplements with prescription medications.

Conclusion

NAD+ is a vital enzyme for cellular energy production, communication, and DNA repair. As we age, NAD+ levels become more important than ever.  We can potentially slow the decline in age-related conditions, improve immune support, cognitive function, and overall longevity.

With EllieMD, you can understand the science and strategies of boosting NAD+, and unlock the power of NAD+ for a healthier life of vitality and energy.