Understanding NAD+ and Its Importance
NAD+, or nicotinamide adenine dinucleotide, is one of the body's most essential and abundant molecules, found in all living cells and essential for life. This makes NAD+ a prerequisite and integral to numerous cellular processes like DNA repair, energy metabolism, and immune cell function.(1)
The body’s heavy reliance on NAD+ creates a constant cycle of synthesis, recycling, and breakdown,(1) so NAD+ precursors are needed in adequate supply to maintain the high activity.(2)
Without the extra supplies needed for NAD+ production, the body has less and produces less, energy to complete critical biological processes, undergoing stress that can lead to cellular dysfunction and impaired DNA repair, causing various health implications.(1)
As you age, NAD+ levels steadily decline and have been linked to increased risk (3) of age-related diseases like metabolic disorders and compromised immune function.(4) Environmental factors also significantly affect levels, and understanding the mechanisms of NAD+ production can help you optimize your health regimen.
Simply put; maintaining NAD+ levels is necessary for supporting and extending a healthy lifespan.
Types of NAD+ Boosting Supplements
Boosting supplements are the most efficient way to boost NAD+ levels and have been extensively researched for safety and efficacy, particularly as natural production declines with age and environmental stress. These supplements are formulated with precursor products to NAD+ synthesis that stimulate production to increase intracellular levels.(5)
Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are the most studied and widely used NAD+ precursors. Both compounds are converted into NAD+ through different pathways but efficiently work to increase levels. Incorporating NR or NMN into your daily regime can support NAD+ decline and overall health as you age.(6)
Maximizing The Benefits
Well Balanced Diet
NAD+ facilitates the extraction of metabolic energy from food and conversion into cellular energy as adenosine triphosphate (ATP). Niacin or vitamin B3 contains precursors required for NAD+ synthesis, and eating/consuming a diet rich in B3 foods can provide extra resources/nutrients for boosting production.(7)
Many animal-based foods like meat and fish contain niacin in highly bioavailable forms, while certain plant-based foods like legumes and whole grains contain smaller but still notable amounts of B3.(8)
Conversely, high fat and sugar diets deliver excess amounts of energy that overload cells and disrupt mitochondria function. Damaged mitochondria can affect the body’s ability to maintain NAD+ production causing lower production and deplete reserves.(9)
Exercise
Exercise creates healthy stress in the body to activate repair and recovery pathways. Muscles signal they need more energy in the form of ATP while activating sirtuin cellular stress responders, and both stimulate NAD+ production.(10)
The increased demand enhances NAD+ processes and upregulates nicotinamide phosphoribosyltransferase (NAMPT), the enzyme that determines the rate of NAD+ synthesis. Exercise increases NAMPT protein expression, which enhances the body’s ability to produce and sustain NAD+ levels.(11)
Fasting
Intermittent fasting and reduced caloric intake may have the ability to enhance NAD+ processes. Energy stress within cells, when deprived of external food energy, stimulates NAD+ synthesis to produce extra energy in the mitochondria. Fasting-induced NAD+ synthesis can support cellular energy and metabolic health.(12)
Geroprotective Compounds: Exploring the Synergy
NAD+ precursors, like NMN and NR, can be used alongside certain age-extending compounds that work synergistically to increase NAD+ levels.
- Stilbenes like resveratrol and pterostilbene are naturally occurring compounds in grapes and berries that have been studied in combination with NMN and were found to increase skeletal muscle NAD+ stores while possessing anti-inflammatory and antioxidant characteristics.(13)
- Coenzyme Q10 (CoQ10), similarly declines with age and works in tandem with NAD+ to support mitochondrial function and energy metabolism. When supplemented with precursors, CoQ10 can enhance NAD+ production and promote healthy aging.(13)
- Betaine, a compound derived from beetroot, aids in the metabolism of NAD+ precursors and contains strong anti-inflammatory properties. Betaine supports NAD+ synthesis while reducing cellular stress by suppressing inflammatory pathways(13) that become overactive with aging and accelerate NAD+ decline.(14)
- Flavonoids, such as quercetin, luteolin, and apigenin, work as CD38 inhibitors preventing NAD+ degradation. These molecules preserve and increase NAD+ levels by limiting access for enzymes that break down NAD+ stores.(15)
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The carotenoids, astaxanthin, and lycopene, are antioxidants that can boost NAD+ levels and activate cellular pathways that enhance NAD+ synthesis. By increasing sirtuin protein activity,(13) carotenoids drive the NAD+ consumption loop, consuming and producing, more efficiently.(16)
Causes of Decline
Aging
As you age, NAD+ naturally declines in muscle tissues as aging affects the pathways that synthesize NAD+. CD38 is a protein with enzymatic activity that plays a critical role in maintaining cellular homeostasis and supporting immune function. As the body ages, various processes naturally slow down and become less efficient, increasing the reliance on proteins like CD38 to sustain healthy function.
However, CD38 consumes NAD+ as fuel, and its increased activity leads to higher NAD+ consumption. With aging, the body's ability to regenerate NAD+ diminishes, creating an imbalance. This direct relationship between CD38 activity, aging, and NAD+ consumption explains the natural decline in NAD+ levels over time.(17)
DNA damage
A key function of your NAD+ is fueling enzymes that make repairs. Damaged DNA creates a request signal for repairs to be made that are powered by NAD+. More damage means more NAD+ needs to be available for consumption to problem solve within the body.(18)
Avoiding smoking, which contains harmful chemicals that bind directly to your DNA,(19) and excess sun exposure, which damages the DNA replication through the skin,(20) can mitigate requests for repairs and, in turn, for NAD+ stores.
Alcohol
Alcohol consumption heavily reduces NAD+ levels due to the expensive metabolization process. The liver requires a significant amount of NAD+ to detoxify, making stores unavailable for standard processes (to activate sirtuins). Avoiding alcohol comes with the added benefits of improved sleep and mood.(2)
Conclusion
NAD+ plays an essential role in maintaining cellular health, supporting energy production, and enabling vital biological processes like DNA repair and immune function. While aging and environmental factors naturally deplete NAD+ levels, taking proactive steps to maintain or boost NAD+ status can significantly enhance your overall health.
Incorporating a balanced diet, regular exercise, and minimizing factors that cause NAD+ decline, such as alcohol, smoking, and prolonged stress, can effectively work to support and protect the body’s natural reserves.
By integrating these strategies into your routine, you can maximize the benefits of NAD+, promote resilience against age-related decline, and support a healthier, more vibrant lifespan.