The Research
NAD+ The Research
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The Discovery
1906 was the year, Sir Arthur Harden and William John Young were first to identify NAD+. The two aimed to better understand fermentation — in which yeast metabolise sugar and create alcohol and CO2.
It had taken nearly 20 years for NAD+ to gain further 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.”
Known for “the Warburg effect” — Otto Heinrich Warburg — further pushed the science forward in the 1930s, with research explaining NAD+ playing a role in metabolic reactions. Conrad A. Elvehjem and C.K. Koehn identified in 1931, 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.
In the next decade, Arthur Kornberg, who won the Nobel Prize for showing how DNA and RNA are formed, discovered NAD synthetase, the enzyme that makes NAD+. This research initiated the beginning of understanding the building blocks of NAD+.
Scientists Jack Preiss and Philip Handler in 1958, 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 further helped scientists understand the role of NAD+ in the diet. Handler’s work focused largely on malnutrition and its role in disease, including pellagra, which then later earned him the National Medal of Science from President Ronald Reagan, who cited Handler’s “outstanding contributions to biomedical research...furthering the state of American science.”
Scientists now realised that NAD+ played a crucial role in overall health, but 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 has ultimately encouraged scientists to study NAD+ as a part of the ageing process and health benefits.
