What is NAD+ and Why Is it Important?

How NAD+ Is Powerful

Open any biology textbook and you’ll learn about NAD+, which stands for nicotinamide adenine dinucleotide. It’s a critical coenzyme found in every cell in your body that’s involved in hundreds of metabolic processes like cellular energy and mitochondrial health. NAD+ is hard at work in the cells of humans and other mammals, yeast and bacteria, even plants.

Scientists have known about NAD+ since it was first discovered in 1906, and since then our understanding of its importance has continued to evolve. For example, the NAD+ precursor niacin played a role in mitigating pellagra, a fatal disease that plagued the American south in the 1900s. Scientists at the time identified that milk and yeast, which both contain NAD+ precursors, alleviated symptoms. Over time scientists have identified several NAD+ precursors — including nicotinic acid, nicotinamide, and nicotinamide riboside, among others — which make use of natural pathways that lead to NAD+. Think of NAD+ precursors as different routes you can take to get to a destination. All the pathways get you to the same place but by different modes of transportation.

Recently, NAD+ has become a prized molecule in scientific research because of its central role in biological functions. The scientific community has been researching how NAD+ relates to notable benefits in animals that continue to inspire researchers to translate these findings to humans. So how exactly does NAD+ play such an important role? In short, it’s a coenzyme or “helper” molecule, binding to other enzymes to help cause reactions on the molecular level.

But the body doesn’t have an endless supply of NAD+. In fact, it actually declines with age.

The history of NAD+ research, and its recent establishment in the science community, has opened the floodgates for scientists to investigate maintaining NAD+ levels and getting more NAD+.

What is the History of NAD+?

NAD+ was first identified Sir Arthur Harden and William John Young in 1906 when the two aimed to better understand fermentation — in which yeast metabolize sugar and create alcohol and CO2. It took nearly 20 years for more NAD+ recognition, when Harden shared the 1929 Nobel Prize in Chemistry with Hans von Euler-Chelpin for their work on fermentation. Euler-Chelpin identified that the structure of NAD+ is made up of two nucleotides, the building blocks for nucleic acids, which make up DNA. The finding that fermentation, a metabolic process, relied on NAD+ foreshadowed what we now know about NAD+ playing a critical role in metabolic processes in humans.

Euler-Chelpin, in his 1930 Nobel Prize speech, referred to NAD+ as cozymase, what it was once called, touting its vitality. “The reason for our doing so much work on the purification and determination of the constitution of this substance,” he said, “is that cozymase is one of the most widespread and biologically most important activators within the plant and animal world.”

Otto Heinrich Warburg — known for “the Warburg effect” — pushed the science forward in the 1930s, with research further explaining NAD+ playing a role in metabolic reactions. In 1931, the chemists Conrad A. Elvehjem and C.K. Koehn identified that nicotinic acid, a precursor to NAD+, was the mitigating factor in pellagra. United States Public Health Service Doctor Joseph Goldberger had previously identified that the fatal disease was connected to something missing in the diet, which he then called PPF for “pellagra preventive factor.” Goldberger died before the ultimate discovery that it was nicotinic acid, but his contributions led to the discovery, which also informed eventual legislation mandating the fortification of flours and rice on an international scale.

The next decade, Arthur Kornberg, who later won the Nobel Prize for showing how DNA and RNA are formed, discovered NAD synthetase, the enzyme that makes NAD+. This research marked the beginning of understanding the building blocks of NAD+. In 1958, the scientists Jack Preiss and Philip Handler defined what’s now known as the Preiss-Handler pathway. The pathway shows how nicotinic acid — the same form of vitamin B3 that helped cure pellagra — becomes NAD+. This helped scientists further understand the role of NAD+ in the diet. Handler later earned the National Medal of Science from President Ronald Reagan, who cited Handler’s “outstanding contributions to biomedical research...furthering the state of American science.”

While scientists had now realized the importance of NAD+, they had yet to discover its intricate impact on a cellular level. Forthcoming technologies in scientific research combined with comprehensive recognition of the coenzyme’s importance ultimately encouraged scientists to continue studying the molecule.

The Future of NAD+

For nearly 100 years, NAD+ has been incredibly important, but the gradual pace of scientific research and technological development has only now begun to reveal how it can be utilized.

Knowing the history of NAD+ and subsequent discoveries around the coenzyme has led researchers to explore what the science community can now do with the information. NAD+ has enormous potential and how it will be fulfilled is the most exciting aspect of current research.

A human study from 2017, conducted by Elysium Health, found that daily doses of an NAD+ precursor increased NAD+ levels by an average of 40 percent. Recent studies evaluating the effects of NAD+ precursors in animals show promise, but to date there is not yet evidence that these animal studies can be extrapolated to humans