The human body contains approximately 37 trillion cells. Each of these billions of cells relies on NAD+
to fulfill its physiological responsibilities. This molecule maintains the normal operation of the organism. Without NAD+, the heart cannot pump blood, the lungs cannot inhale air, and brain neurons cannot generate signals. We can say that without this crucial molecule, all vital organs would cease to function. NAD+ acts like fuel for a car, providing power for the stable functioning of the human body. David Sinclair, Co-Director of the Center for the Biology of Aging at Harvard Medical School, stated: “NAD+ serves as a core substance for maintaining a youthful state and sustains life activities. Without it, the human body would lose vital signs within 30 seconds.”
I. What is the Nature of NAD+?
To understand the role of NAD+, it is first necessary to clarify the core concept of NAD. NAD is the abbreviation of nicotinamide adenine dinucleotide, which is a type of coenzyme. As an essential component that assists various enzymes in catalyzing redox reactions, it mainly undertakes the function of electron transfer in the human body.
Based on whether it carries electrons to be transferred, NAD can exist in two forms: NAD+ and NADH. Among them, NADH is in the reduced state, while NAD+ is in the oxidized state. These two forms are like the two sides of a coin; they have similarities yet also possess unique and irreplaceable roles. The core difference between them is that NADH carries one more positively charged hydrogen atom (H) and two negatively charged electrons than NAD+. Since these two forms can be converted into each other in the human body, NAD+ is often used to refer to the entire NAD system in daily expressions.
NAD+ also has another name – Coenzyme I, and its full name is nicotinamide adenine dinucleotide. It is widely distributed inside all cells of the human body, participates in thousands of biological catalytic reactions, and is an indispensable coenzyme in the human body. Fluctuations in NAD+ levels may directly affect the status of other key functions of the body and are closely related to the human aging process.
II. What Roles Does NAD+ Play in the Human Body?
NAD+ and NADH participate in aerobic glucose metabolism in cells. They provide energy for life activities and support human behavioral functions. Aerobic glycolysis mainly includes three links: glycolysis, the tricarboxylic acid cycle, and the electron transport chain.
The Energy Power Station
During glycolysis and the tricarboxylic acid cycle, NAD+ acts like a “transport train.” It receives electrons to become NADH. Then, it transports these electrons and biological hydrogen to the electron transport chain on the inner mitochondrial membrane. Oxidative phosphorylation immediately follows, producing three ATP molecules. ATP serves as the main energy source and storage form in the body.
Synthesis and Aging
The body evolved two pathways to supply NAD+: the de novo synthesis pathway and the salvage synthesis pathway. However, aging renders these pathways ineffective. As the body ages, NAD+ content inevitably decreases.
The Chini team at Mayo Clinic published a review in Aging Cell on July 9, 2023. They pointed out that an oxidase called IDO1 becomes abnormally activated during aging. This breaks down L-tryptophan, a key raw material for NAD+ synthesis. Furthermore, the content of NAMPT (a rate-limiting enzyme) and NMNAT (a key transferase) gradually decreases. Cells must also consume additional NAD+ to repair damaged components. For example, the DNA repair enzyme PARP1 consumes large amounts of NAD+ to fix age-related DNA damage.
Thousands of Biochemical Reactions
Studies confirm that this compound participates in thousands of reactions, including:
- Improving energy supply via the tricarboxylic acid cycle (TCA).
- Activating longevity genes through the Sirtuins pathway.
- Repairing DNA damage via the PARPs pathway.
- Maintaining nuclear-mitochondrial signaling to slow senescence.
- Inhibiting lipid peroxidation to protect mitochondria.
- Promoting dopamine synthesis to support Parkinson’s patients.
- Regulating norepinephrine and serotonin to alleviate depression.
- Managing autoimmune diseases by adjusting immune responses.
Hassina Massudi and her team from the University of New South Wales found that low levels associate with age-related changes. Data shows that levels decrease by 50% between the ages of 40 and 60.
III. What Harms Does a Decrease in NAD+ Levels Bring?
The body’s internal level directly determines the rate of the aging process. Abnormal changes in homeostasis appear in almost all age-related diseases, including neurodegeneration, diabetes, and cancer.
Cardiovascular and Metabolic Risks
The Chini team noted that abnormal metabolism represents a risk factor for cardiovascular diseases. Decreased levels affect heart energy supply, disrupting normal pumping functions. In diseases like cancer and fibrosis, metabolic disorders act as pathological mechanisms.
Core Mechanisms of Aging
In 2019, the textbook Biochemistry and Cell Biology of Ageing concluded that the core mechanisms of aging involve two factors: oxidative free radical damage and decreased molecular levels. Fortunately, restoring these levels can alleviate or reverse many age-related diseases.
IV. What Effects Does Supplementing NAD+ Have?
In February 2021, scholars from the Buck Institute for Research on Aging published findings in Nature Reviews Molecular Cell Biology. They showed that directly supplementing absorbable NAD+ brings positive benefits to the brain, cardiovascular system, liver, and muscles.
Potential Therapeutic Value
A paper in Translational Medicine of Aging stated: “Supplementing NAD+ can address aging and various diseases, improving quality of life for the elderly.” In 2021, researchers compared NADH and NMN and found NADH more effective in increasing NAD+ levels. Additionally, NADH promotes alcohol metabolism.
In July 2021, Cambridge researchers published a paper in Cell Death & Disease. They found that people taking NAD+ precursors maintain a lower risk of Alzheimer’s disease. Furthermore, a University of Wisconsin-Madison team proved in Nature Nanotechnology (2022) that NADH-loaded nanoparticles improve sepsis therapy by modulating immune homeostasis.
Organs Benefiting from Increased NAD+
- Brain: Optimizes function and prevents degeneration.
- Vascular System: Promotes new blood vessel formation.
- Liver: Reduces hepatic steatosis and enhances regeneration.
- Muscles: Reduces atrophy and enhances physical activity.
- Pancreas: Improves β-cell function and insulin secretion.
- Adipose Tissue: Prevents insulin resistance.
- Inflammation: Improves immune cell function.
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