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Dr. David A. Sinclair

Harvard Medical School

Discovery of NAD+


William Young and Sir Arthur Harden first discovered NAD+ in 1906 when trying to understand the fermentation process. This is when yeast metabolises sugar to create alcohol. It was not until 20 years later there was recognition for their work in fermentation. Harden shared the 1929 Nobel Prize for Chemistry with Hans von Euler-Chelpin. It was Euler-Chelpin who found NAD+ has a structure of two nucleotides and these are what forms DNA. The findings were an important breakthrough. It showed the metabolic process for fermentation relied on NAD+ and the vital role NAD+ has in the human metabolic process. When giving his Nobel Prize acceptance speech, Euler-Chelpin said the discovery was one of the most important biological activators in in animals and plants.


In the 1930s, Otto Heinrich Warburg did further research into the role NAD+ has how the metabolic system functions. The next year, two chemists found nicotinic acid is a precursor to NAD+. This was the missing factor that causes pellagra. This is a severe condition that ravaged 200,000 people in the America’s south in the late 1920s. United States Public Health doctor Joseph Goldberger identified the cause of this fatal disease was a lack of something lacking in people’s diet. And, discovered brewer’s yeast was a cheap cure to pellagra. He was right but died before the discovery nicotinic acid was the missing factor. It was his thoughts about the matter that helped lead to the discovery.

During the 1940s, biochemist Arthur Kornberg discovered the enzyme that creates NAD+. His research became the foundation for a better understanding of NAD+. In 1959 he won a Nobel Prize in Physiology or Medicine for discovering how DNA and RNA forms. In 1958 that scientists, Jack Preiss and Philip Handler, discovered how nicotinic acid becomes NAD+ using the same form of vitamin B3 used to help cure pellagra. Handler’s focus was on malnutrition and how it affects different diseases. His work helped scientists to further understand the importance of NAD+ to the diet. This work earned him a National Medal of Science for his contribution to biomedical research. Although the importance of NAD+ to human health is well known, scientific research has been gradual. NAD+ has a lot of potential for replenishing NAD+ levels in humans to help a vast range of chronic conditions.

Treatment of Alzheimer's disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study.

2004; 30(1): 27-33: Drugs under experimental and clinical research.
Authors: Demarin V, Podonik SS, Storga-Tomic D, Kay G.

The Effects of Nicotinamide Adenine Dinucleotide (NAD) on Brain Function and Cognition (NAD)

U.S. National Library of Medicine

Genetic Variants in Nicotinamide Adenine Dinucleotide (NAD) Synthesis Pathway

U.S. National Library of Medicine

Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults

2018; 9(1286): 1-11: Nature Communications
Authors: Martens CR, Denman BA, Mazzo MR, Armstrong ML, Reisdorph N, McQueen MB, Chonchol M, Seals DR.

NAD+ and sirtuins in aging and disease

2014; 24(8): 464-71: Trends in Cell Biology
Authors: Imai, S & Guarente, L.

Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes

2018; 30(2): 251-294: Antioxidants & Redox Signaling
Authors: Braidy N, Berg J, Clement J, Khorshidi F, Poljak A, Jayasena T, Grant R, & Sachdev P.

Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases

2017; 13(4): 213-225: Nature Reviews Nephrology
Hershberger KA, Martin AS, & Hirschey MD.

Study to Evaluate the Effect of Nicotinamide Riboside on Immunity

U.S. National Library of Medicine

NAD Therapy for Improving Memory and Brain Blood Flow in Older Adults With Mild Cognitive Impairment

U.S National Library of Medicine

The Founders of NAD+ Therapy

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