The History of Nicotinamide Mononucleotide and NAD+

Nicotinamide adenine dinucleotide (NAD+) is considered a critical molecule for human life, given its versatility. It plays an integral role in providing cells with energy; almost all biological processes require NAD. For this reason, Nicotinamide Mononucleotide has become the focus of biological research in recent times.

A “factor” that stimulates the fermentation of sugar into alcohol was discovered by William John Young and Arthur Harden in liquid extracted from brewer’s yeast in 1906. This factor was given the name of “co-ferment” at that time and is now known by us as NAD. Harden, with help from Hans von Euler-Chelpin, decided to dig deeper into the topic of fermentation. Having developed an in-depth understanding of NAD, they were awarded with a Nobel Prize in 1929.

New developments in NAD studies were also seen in the 1930s under Nobel laureate Otto Warburg, who discovered its part in assisting several biochemical processes. He found that NAD works for electrons as a kind of relay.

Biochemical reactions are powered by electron transfer between molecules. Conrad Elvehjem along with his University of Wisconsin colleagues, in 1937, found that NAD+ supplements could treat dogs with pellagra or “Black Tongue.” The symptoms in humans range from diarrhea, mouth sores to dementia. It occurs due to a deficiency of niacin and is treated with nicotinamide, a precursor to Nicotinamide Mononucleotide. Another research that proved to be essential towards understanding NAD+ was Arthur Kornberg’s. Throughout the ’40s and ’50s, his research led him to discover RNA transcription and DNA replication principles.

In 1958, Philip Handler and Jack Preiss found the biochemical stages involved converting nicotinic acid into NAD. These steps are now known as “Preiss-Handler Pathway”.  Mandel, Weill, and Chambon, in 1963, found that Nicotinamide Mononucleotide activates a vital nuclear enzyme by creating the cellular energy needed by it. This finding formed the basis for a further string of discoveries on a kind of protein known as PARP. This protein plays a crucial role in cell death regulation and repairing DNA damage. Its activity is also linked to changes in lifespan.

Soon in the year 1976, Rechsteiner and his fellow scientists stumbled upon convincing evidence that suggested NAD+ to have “other major functions” in cells of mammals, something more than its traditional role of an energy providing coenzyme.

With the help of this discovery, Leonard Guarente and his colleagues were able to find that proteins known as sirtuins can prolong lifespan by utilizing NAD by turning certain genes “silent.”

This study showing the potential of NAD and its intermediaries like Nicotinamide Mononucleotide, and NR, to enhance and uplift many age-related issues gave new hope to researchers and quickly became a topic of interest.

What Does the Future Hold For Nicotinamide Mononucleotide?

Thanks to the promising results that Nicotinamide Mononucleotide has shown in animal studies, the next big step for the researchers is to understand how the Nicotinamide Mononucleotide molecule functions in humans to show therapeutic results. Recently in Japan, a clinical trial demonstrated that Nicotinamide Mononucleotide is safe for humans at the current dosage. Further research and trials in human beings will be needed and are being planned. Nicotinamide Mononucleotide is a mysterious and wonderful molecule from which we can gain access to a plethora of benefits. But there is still a lot more that needs to be learned.

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