Introducing our ultimate stack to boost NAD levels:

NR
Apigenin
TMG

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NR

Nicotinamide Riboside (NR) is an exciting molecule in the Longevity space due to its potential to increase levels of nicotinamide adenine dinucleotide (NAD+) in the body. NAD+ is a coenzyme that plays a crucial role in various cellular processes, including energy metabolism, DNA repair, and regulation of gene expression. NR is a precursor to NAD+ and helps boost NAD+ levels through the following mechanisms:

Sirtuin Activation: NAD+ is a coenzyme required for the activity of sirtuins, a class of enzymes that play a role in various cellular functions, including DNA repair, metabolism, and longevity. Higher NAD+ levels can potentially enhance the activity of sirtuins, leading to benefits associated with their functions.

Energy Metabolism: NAD+ is a key player in cellular energy metabolism, particularly in the mitochondria, the energy-producing structures within cells. By increasing NAD+ levels, NMN may help support mitochondrial function and overall energy production.

DNA Repair: NAD+ is involved in DNA repair processes, which help maintain the integrity of the genetic material within cells. Adequate NAD+ levels are essential for efficient DNA repair mechanisms.

Anti-Aging Potential: Some research suggests that declining NAD+ levels may be associated with the aging process and age-related diseases. By increasing NAD+ levels, NMN has been proposed as a potential intervention to counteract age-related decline in cellular functions.

Redox Regulation: NAD+ is involved in redox reactions within cells, helping to balance oxidative and reductive processes. This can have implications for cellular health and protection against oxidative stress, which is linked to aging and various diseases.

Apigenin

While NMN can help rejuvenate our NAD levels, we must also take into account the influence of an enzyme known as CD38 in the process. As we grow older, the activity of CD38 escalates, leading it to consume our valuable NAD resources, thus hindering their integration into the cellular energy cycle.

Recent research conducted by the Buck Institute has shown the root cause of this, attributing it to age-associated inflammation. This process, referred to as 'inflammaging', is intricately linked to the actions of immune cells called 'macrophages' that attempt to counteract age-related deterioration. Tackling this challenge requires the expression of CD38 enzymes within this process.

Apigenin is a flavonoid compound found in certain foods and has been studied for its potential health benefits, including antioxidant and anti-inflammatory properties. Apigenin acts to suppress CD38 activity within cells, thereby fostering a rise in NAD+ levels.

NAD Degradation: CD38 is primarily known for its role in the degradation of NAD+. It enzymatically cleaves NAD+ into nicotinamide and ADP-ribose, which are precursor molecules that can be further metabolized. This process is part of the cellular regulatory system that helps manage NAD+ levels.

NAD Recycling: While CD38 contributes to the breakdown of NAD+, it also participates in the salvage pathway for NAD+ synthesis. The breakdown products generated by CD38, such as nicotinamide and ADP-ribose, can be used by cells to synthesize new NAD+ molecules through the NAD salvage pathway.

Aging and NAD Depletion:CD38 activity has been associated with aging-related NAD+ depletion. As we age, CD38 activity may increase, leading to increased degradation of NAD+. This reduction in NAD+ levels can have implications for cellular health and the aging process. Strategies that inhibit CD38 activity or boost NAD+ synthesis, such as supplementation with NAD precursors like NMN or NR, have been explored as potential interventions for age-related health issues.

Immunomodulation: CD38 is also involved in immune cell function and regulation. It plays a role in calcium signaling and the release of inflammatory molecules. CD38 inhibitors are being investigated for their potential to modulate immune responses and manage inflammatory conditions.

TMG

Trimethylglycine (TMG), also known as betaine, is a naturally occurring compound found in various foods. It has been studied for its potential health benefits, including its role in supporting NMN and NAD+ levels in the body. Here's how TMG contributes to NMN and NAD+ metabolism:

Methylation Support: TMG is involved in a biochemical process called methylation, which is essential for various cellular functions. Methylation reactions are involved in the synthesis of molecules like NMN and NAD+. TMG can provide methyl groups that are used in the conversion of different compounds, potentially supporting the production of NMN and NAD+.

Conversion of Homocysteine: TMG plays a role in the methionine cycle, a process that converts homocysteine (an amino acid) into methionine. This cycle is closely linked to NAD+ metabolism because one of the intermediates, S-adenosylmethionine (SAM), is required for NAD+ synthesis.

NAD Salvage Pathway:TMG may indirectly support the NAD salvage pathway. This pathway involves the recycling of nicotinamide (a breakdown product of NAD) back into NAD+ through a series of enzymatic reactions. The availability of methyl groups from TMG can influence these reactions and contribute to NAD+ synthesis.

DNA Methylation and Repair:

Adequate methylation is crucial for DNA methylation and repair processes, which are linked to cellular health. These processes are also associated with NAD+ levels. TMG's role in methylation can indirectly contribute to maintaining DNA integrity and supporting NAD-dependent DNA repair mechanisms.

Mitochondrial Function: TMG can affect mitochondrial function and energy metabolism. Healthy mitochondria are vital for efficient NAD+ production and cellular energy production.

The Ultimate NAD Support Bundle