Professor Johan Auwerx and colleagues from the Ecole Polytechnique Federale de Lausanne in Switzerland have published a review in Nature entitled “NAD+ Homeostasis in Health and Disease”, which reviews in detail the basic knowledge of NAD+ biochemistry and metabolism. The role and translational potential of NAD+ in disease treatment were discussed.
What is NAD+?
NAD+ was first discovered while studying the metabolic rate of yeast extracts, and was first discovered in 1904 by British biochemist Sir Arthur Haddon.
Harden awarded the 1929 Nobel Prize in Chemistry for this discovery.
Nicotinamide adenine dinucleotide (NAD+) is a coenzyme in REDOX reactions, making it central to metabolism.
NAD+ directly or indirectly affects many key cellular functions, including metabolic pathways, DNA repair, chromatin remodeling, cell aging, and immune cell function.
These cellular processes and functions are essential for maintaining tissue and metabolic homeostasis and healthy aging.
What does NAD+ do?
NAD+ is a key metabolite and coenzyme in a variety of metabolic pathways and cellular processes, providing the body with the energy necessary for survival and supporting all human behaviors.
Cellular aerobic glucose metabolism consists of three parts: glycolysis, tricarboxylic acid cycle and electron transport chain.
NAD+ is essential for maintaining health and balance throughout the body and is widely used as a cofactor or substrate for biochemical reactions, with more than 300 enzymes operating on NAD+.
NAD+ is a mediator for critical cellular functions and adaptation to metabolic needs.
Metabolism, REDOX, maintenance and repair of DNA, gene stability, and epigenetic regulation all require the involvement of NAD+.
With age, NAD+ levels in tissues and cells gradually decline.
Decreased levels of NAD+ causally linked to a number of diseases associated with aging, including cognitive decline, cancer, metabolic diseases, sarcopenia, and frailty.
What are the dangers of declining NAD+ levels?
The level of NAD+ in the body determines the rate of the aging process, and changes in environmental homeostasis within NAD+ found in almost all age-related diseases, including neurodegenerative diseases, diabetes, and cancer.
The Mayo Clinic review in “Mechanisms of NAD+ : Role in Cellular Senescence and senescence” points out that NAD+ metabolic dysfunction is an important symptom and risk factor for cardiovascular disease, and reduced levels of NAD+ will affect the heart’s energy supply, which in turn disrupts the heart’s pumping function.
Low NAD+ levels damage normal DNA, interfere with protein synthesis, induce mitochondrial dysfunction, and promote cellular aging processes, including atherosclerosis, arthritis, hypertension, cognitive decline, diabetes, and cancer. NAD+ related metabolic disorders are also important pathological mechanisms.
In 2019, Biochemistry and Cell Biology of Aging summarized decades of aging research and attributed the aging mechanism to two main causes: oxidative free radical damage and decreased NAD+ levels.
Numerous studies have shown that decreased NAD+ levels causally linked to many age-related diseases, including cognitive decline, inflammation, cancer, metabolic diseases, sarcopenia, neurodegenerative diseases, and many of these age-related diseases can slowed or even reversed by restoring NAD+ levels.
Why is NAD+ produced by supplementing NMN
As shown in the figure, NAD+ composed of two nucleotides linked by a phosphate group.
These two nucleotides are AMP and NMN.
An AMP made of adenosine (green), a ribose ring (blue), and a phosphate group (orange) combines with an NMN made of a ribose ring, a phosphate group, and a nicotinamide (NAM) (pink) to form NAD +.
NAD+ a very large phosphorylated molecule with too large molecular weight and unstable structure, and the human body cannot directly absorb and utilize NAD+.
Because direct supplement of NMN is the best way to supplement NAD+, this is also the reason why scientists have shifted their research focus to its precursor substance – NMN.
Among the many NAD + precursor supplements, NMN is also the most popular.
How is NMN generated?
The generation process of NMN is complicated and mainly includes the following steps:
- 1. NAMAT enzyme converts NAM (nicotinamide) to NA (nicotinic acid) through catalytic reaction;
- 2. in red blood cells, PBE enzyme converts NA into NAMN (nicoyladenine nucleoside);
- 3. After a series of complex reactions, NAMN finally generates NMN, completing the transformation from NAM to NMN.
Method of intravenous drip of NMN
NMN (nicotinamide mononucleotide) is one of the precursors of NAD+ and can directly converted by the body into NAD+.
Through the way of intravenous drip, NMN can directly delivered into the blood, thereby rapidly increasing the level of NAD+ in the body.
The advantages of intravenous drips
Intravenous drip is a method of delivering drugs or nutrients directly into the bloodstream, which bypasses the digestive system and ensures rapid absorption and utilization of the drugs or nutrients.
For situations where NAD+ levels need to increased quickly, intravenous drip is an effective method.
Transformation of NMN
Once NMN enters the bloodstream, its quickly absorbed by cells and converted to NAD+.
This process does not require additional enzymatic reactions, so NMN considered a highly effective NAD+ supplement.
Why does intravenous NMN supplement NAD+ better than oral NMN
The effect of intravenous drip NMN in supplementing NAD+ is better than oral NMN for the following reasons:
1. High absorption efficiency:
Oral NMN needs to digested and absorbed through the gastrointestinal tract,
while intravenous drip can directly enter the blood circulation system,
bypassing the digestive process of the gastrointestinal tract, so the absorption efficiency is higher.
2. Action speed is fast:
Intravenous drips can quickly deliver NMN to target tissues and organs, thereby exerting its biological effects more quickly.
In contrast, oral NMN needs to go through multiple steps such as intestinal absorption and liver metabolism, and the action time is relatively long.
3. Good dose control:
Intravenous drip can be accurately controlled according to the specific situation and needs of patients, while oral NMN dose affected by a variety of factors, such as individual differences, dietary habits, and so on, is difficult to achieve accurate control.
such as individual differences, dietary habits, and so on, is difficult to achieve accurate control.
4. High security:
The risk of NAD+ supplementation with intravenous drip NMN is low because it does not need to metabolized by the liver,
avoiding problems such as liver damage that can caused by oral NMN.
Intravenous drips can also reduce interactions between drugs and other substances, improving the safety and effectiveness of treatment.
