What is NMN?

Below is a summarised, simplified comprehensive guide on NMN by GroovyNMN with credit to https://www.nmn.com/what-is-nmn

What is NMN?

Nicotinamide Mononucleotide (NMN) is a naturally occurring molecule found in all living cells and is a precursor to NAD+ (Nicotinamide Adenine Dinucleotide), a vital coenzyme involved in energy production and DNA repair. Structurally, NMN consists of a phosphate group, ribose sugar, and nicotinamide base. By converting into NAD+, NMN helps boost cellular energy, supports metabolic health, and combats the effects of aging, which is why it’s commonly referred to as an NAD+ booster.

The Importance of Boosting NAD+ with NMN

NAD+ is one of the most vital molecules in the body, acting as a coenzyme that powers enzymes responsible for critical processes like energy production and DNA repair. However, NAD+ levels decline with age and in cases of chronic diseases such as obesity, cardiovascular issues, and neurodegeneration.

Restoring NAD+ levels with NMN can potentially slow aging and combat chronic diseases. NAD+ also activates sirtuins, enzymes that protect cells by repairing DNA and supporting mitochondrial health, which may extend lifespan and prevent age-related diseases.

NAD+ and Mitochondrial Health

NAD+ is crucial for mitochondrial energy production, driving metabolic processes like glycolysis and the electron transport chain. It acts as a cellular “recharger,” transferring electrons to maintain energy flow and regulate enzyme activity, gene expression, and cell signaling.

NAD+ in DNA Repair

As we age, DNA damage accumulates due to environmental factors, and repairing this damage uses up NAD+. Proteins like PARP, which are involved in DNA repair, depend on NAD+ to function. With age, NAD+ levels decrease, making cells less efficient at repairing DNA damage, which accelerates aging. NMN helps replenish NAD+ levels, supporting DNA repair and protecting cells from further damage.

How to Boost NAD+ Naturally

In addition to NMN, other methods to raise NAD+ levels include caloric restriction, exercise, and consuming polyphenols (plant-based compounds). These strategies can enhance sirtuin activity, contributing to cell protection and promoting overall health.

(Nad.com)

Why is NAD+ Important?

Since its discovery in 1906, NAD+ has been recognized for its essential role in nearly every cellular process. Research shows that boosting NAD+ levels can help with age-related conditions like diabetes, cardiovascular diseases, neurodegeneration, and immune system decline. Animal studies have demonstrated anti-aging properties when NAD+ levels are increased.

Can NMN Help Fight COVID-19?

Emerging research suggests NAD+ boosters like NMN could support the immune system in fighting COVID-19. Scientists believe NMN may help prevent dangerous immune responses, like cytokine storms, in older adults.

Benefits of NAD+ Boosters

• Aging: NAD+ fuels sirtuins, proteins that repair DNA and maintain genome integrity, showing potential to increase lifespan in animal studies.
• Metabolic Health: NAD+ supports healthy mitochondria, helping reduce diet- and age-related weight gain.
• Heart Health: Studies suggest NAD+ boosters can protect against heart disease and improve cardiac function.
• Neurodegeneration: Boosting NAD+ in mice has been shown to enhance brain function and protect against Alzheimer’s disease.
• Immune System: NAD+ is critical for regulating inflammation and improving immune responses, particularly in older adults.

Many of these findings are based on animal studies, but scientists are actively exploring how they may translate to humans.

How Does the Body Make Nicotinamide Adenine Dinucleotide (NAD+)?

The body produces NAD+ from smaller building blocks called precursors. These include tryptophan, nicotinamide (Nam), nicotinic acid (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). NMN is one of the last steps in NAD+ synthesis.

There are two main pathways for NAD+ production:

1. De novo pathway: Produces NAD+ from scratch, starting with tryptophan.
2. Salvage pathway: Recycles degraded NAD+ components to make new NAD+, similar to a biological recycling process.

Both pathways help maintain healthy NAD+ levels for cellular energy and repair.

NAD+ Biosynthesis from NMN

How is NMN Synthesized in the Body?

NMN is created from vitamin B3 (niacin) in the body through an enzyme called nicotinamide phosphoribosyltransferase (NAMPT). NAMPT combines niacin with PRPP (a sugar phosphate) to produce NMN. NMN can also be derived from nicotinamide riboside (NR) by adding a phosphate group.

Boosting NAD+ Levels

Lower NAMPT levels can reduce NMN production, leading to lower NAD+ levels. Supplements like NMN can help increase NAD+ levels, which is essential for energy production and slowing the aging process.

NMN Supplements and Absorption

NMN is absorbed into cells via a specialized transporter, more efficiently than NAD+, which cannot easily cross cell membranes. NMN supplementation boosts NAD+ in tissues like the liver, muscles, heart, and more within minutes, supporting overall cellular health and longevity.

Methods to Increase NAD+ Naturally

Fasting or calorie restriction boosts NAD+ and sirtuin activity, which has been linked to slowing the aging process. However, NAD+ in food is too low to impact levels significantly, making NMN supplements an effective alternative for boosting NAD+.

NAD+ vs. NAD Precursors

Direct NAD+ supplementation isn’t practical since it cannot easily enter cells. NAD+ precursors, such as NMN and NR, are more readily absorbed and help restore healthy NAD+ levels as we age, supporting overall metabolism and longevity.

NMN is Quickly Converted to NAD+

NMN Side Effects and Safety

NMN has shown to be safe in animal studies, with no toxic effects even at high doses or after long-term (one year) use in mice. Initial human clinical trials have also found NMN to be non-toxic in single doses. One study involving Japanese men noted a slight increase in blood bilirubin levels after NMN intake, though these remained within the normal range. Future research is needed to explore the long-term safety and effectiveness of NMN, but currently, no major side effects have been reported.

The History of NMN and NAD+

1906
Arthur Harden and William John Young discovered a “factor” in yeast that enhanced fermentation, later identified as NAD.

1929
Harden and Hans von Euler-Chelpin were awarded the Nobel Prize for their work on fermentation and NAD’s properties.

1930s
Nobel laureate Otto Warburg identified NAD’s role in electron transfer, crucial for energy in biochemical reactions.

1937
Conrad Elvehjem discovered NAD+ cured pellagra, revealing its importance in human health.

1940s-1950s
Arthur Kornberg’s work on NAD+ led to breakthroughs in DNA replication.

1958
Jack Preiss and Philip Handler detailed the steps converting nicotinic acid to NAD, known as the Preiss-Handler Pathway.

1963
Research by Chambon, Weill, and Mandel showed NMN's role in activating enzymes involved in DNA repair.

1976
Rechsteiner discovered that NAD+ might have additional roles beyond energy transfer, paving the way for Leonard Guarente’s work on sirtuins and lifespan.

Since Then
Interest has grown in NAD, NMN, and NR for their potential to combat age-related conditions and support healthy aging.