The story starts with a jar of yeast juice that would not ferment. In 1906, two chemists in London filtered the life out of it — literally — and in doing so stumbled onto one of the most important molecules in biology. They did not know it at the time. They just knew that fermentation had stopped, and that adding back a boiled, filtered fraction switched it on again. That invisible helper turned out to be NAD+, nicotinamide adenine dinucleotide, a coenzyme now studied in nearly every field of metabolism.
1906: Harden, Young, and the discovery of “cozymase”
Arthur Harden and William John Young were trying to understand how yeast turns sugar into alcohol and carbon dioxide. Working with cell-free yeast extract, they separated it into two parts by dialysis and filtration. Neither part could ferment glucose on its own. Combined, fermentation resumed. The dialyzable fraction was a small, heat-stable molecule — Harden called it a “coferment.” Over the following decades it picked up other names: coenzyme I, and cozymase. That heat-stable fraction is what we now recognise as NAD+ (alongside other cofactors). It was, in effect, the first sighting of the molecule, decades before anyone could say what it was made of.
The work held up. Harden shared the 1929 Nobel Prize in Chemistry for his research on fermentation and fermentative enzymes.
1920s–1930s: Euler-Chelpin and Warburg work out the structure
Knowing something exists is not the same as knowing what it is. That job fell largely to Hans von Euler-Chelpin, who isolated cozymase and worked out its chemical makeup. He shared that same 1929 Nobel Prize with Harden — one for finding the coferment, one for beginning to define it.
The redox story arrived in the 1930s through Otto Heinrich Warburg. Around 1936 he described how the nucleotide coenzyme shuttles hydride from one molecule to another, and identified the nicotinamide portion as the reactive site where the electron transfer happens. This is the function NAD+ is still known for: accepting and donating electrons as cells break down fuel. Warburg’s work also helped establish the dinucleotide structure, correcting earlier assumptions. Between Harden, Euler-Chelpin, and Warburg, the molecule connected to three separate Nobel Prizes — a measure of how central it turned out to be.
Mid-20th century: naming the parts and mapping the pathway
As biochemistry matured, the molecule was renamed from the older “diphosphopyridine nucleotide” (DPN) to nicotinamide adenine dinucleotide (NAD). Researchers including Arthur Kornberg helped clarify how cells actually build NAD through enzymatic steps, part of the broader mid-century effort to map nucleotide biosynthesis. It was slow, unglamorous work, and it laid the groundwork for everything that followed. By this point NAD+ was understood not as a curiosity of yeast, but as a coenzyme running through the metabolism of essentially all living cells.
The precursor side of the story began building too. In 1963, Chambon, Weill and Mandel reported that nicotinamide mononucleotide (NMN) supplied the energy to activate a nuclear enzyme — an observation that led toward the discovery of the PARP family of enzymes and, more broadly, toward understanding NAD+ as more than a metabolic middleman.
2000s–2010s: NMN and the metabolism revival
NMN is a biosynthetic precursor of NAD+ — one of the compounds a cell can convert into the coenzyme. Interest in it climbed as researchers pieced together how NAD+ levels are maintained. In 2004, Revollo, Grimm and Shin-ichiro Imai characterised NAMPT, the rate-limiting enzyme in a key NAD+ synthesis route in mammals, putting NMN squarely on the map as an intermediate worth studying.
The 2010s brought the studies most people now associate with these compounds. In 2011, Yoshino and colleagues reported that NMN affected insulin sensitivity in mice fed a high-fat diet. In 2013, Gomes and colleagues in David Sinclair’s group published work in Cell describing how declining NAD+ disrupts communication between the nucleus and mitochondria in aging mice, and reported that raising NAD+ levels restored certain markers of mitochondrial function in older animals in a sirtuin-dependent way. These are laboratory findings, largely in animal and cell models, and the field remains active and unsettled.
It is worth being honest about where the science sits. NAD+ biology is more than a century old, but the modern questions — how NMN behaves, what it does across human systems, and over what timescales — are still being worked out. Much of the headline research is preclinical. The history is solid; the conclusions are ongoing.
→ NAD+ & NMN Research Guide · COA available NAD+ range
Research use only. NAD+ and NMN are supplied by Vero Labs strictly as research compounds, not for human or animal consumption. They are a coenzyme and its precursor, not peptides, and are intended solely for in-vitro laboratory research and development. Every batch is independently third-party lab-tested for identity and purity, with a published Certificate of Analysis (COA) available for each product.