NAD+ UK: Research, Mechanism and Study Data

Every cell in your body, from the neurons in your brain to the muscle cells in your legs, depends on a single small molecule to turn food into energy. It is called NAD+, and it is one of the oldest and most essential molecules in biology, present in bacteria, plants and animals alike. For most of the twentieth century it was regarded as a humble housekeeping molecule of metabolism. Then, around the turn of the millennium, researchers discovered that it sits at the heart of processes linked to ageing, DNA repair and metabolic health, and that its levels fall as we get older. Since then, NAD+ has become one of the most intensively studied molecules in modern biology.

This guide explains what NAD+ is, how it works, how it was discovered, what the key research has found about it in ageing and metabolism, how the body makes and uses it, and how researchers study it. It is an educational overview of research findings, not medical advice. Crown Peptides supplies NAD+ for laboratory research use only.

What Is NAD+?

NAD+ stands for nicotinamide adenine dinucleotide. It is a coenzyme, a helper molecule that enzymes need in order to work. Structurally, it is made of two nucleotides joined together: one carrying a nicotinamide group, derived from vitamin B3, and one carrying adenine, one of the building blocks also found in DNA and RNA.

Two forms

NAD+ exists in two forms. NAD+ is the oxidised form, ready to accept electrons. NADH is the reduced form, carrying electrons it has picked up. Cells constantly convert one into the other as they break down food and make energy. The ratio between them reflects the cell's metabolic state.

A close relative

NAD+ can also be converted into NADP+, whose reduced form, NADPH, powers antioxidant defences and the building of fats and other molecules. Together, NAD+ and NADP+ form a family at the centre of cellular chemistry.

Is NAD+ a peptide?

No. NAD+ is a nucleotide coenzyme, not a chain of amino acids. It is supplied alongside peptides because it is used in the same research areas, particularly ageing, metabolism and mitochondrial research.

How NAD+ Works

NAD+ has two quite different jobs, and understanding both is the key to understanding why it matters.

Job one: carrying electrons

When cells break down sugars and fats, they release high-energy electrons. NAD+ collects these, becoming NADH, and carries them to the mitochondria, the cell's power stations. There, NADH delivers its electrons to the start of the electron transport chain, where their energy is used to make ATP, the molecule cells use as energy currency. NADH becomes NAD+ again and returns to collect more. In this role, NAD+ is recycled, not used up.

Job two: fuelling signalling enzymes

NAD+ is also consumed as fuel by several families of enzymes that regulate the cell. When these enzymes act, they break NAD+ apart, so it must be constantly remade.

Sirtuins

Sirtuins are enzymes that remove chemical tags called acetyl groups from proteins, including the histone proteins that package DNA. By doing so, they regulate metabolism, stress responses, inflammation and gene activity. Mammals have seven sirtuins, SIRT1 to SIRT7, found in different parts of the cell.

PARPs

PARP enzymes use NAD+ to repair damaged DNA, attaching chains of ADP-ribose that recruit repair proteins. When DNA damage is heavy, PARPs can consume large amounts of NAD+.

CD38 and related enzymes

CD38, found on immune cells and others, breaks down NAD+ and produces signalling molecules involved in calcium regulation. Its activity rises with age and inflammation.

Sirtuins in More Depth

The sirtuins are the part of NAD+ biology that most excites ageing researchers, so they deserve a closer look. The seven mammalian sirtuins live in different parts of the cell. SIRT1, SIRT6 and SIRT7 work mainly in the nucleus, where they regulate genes, DNA repair and the stability of chromosomes. SIRT3, SIRT4 and SIRT5 work in the mitochondria, regulating energy production and fuel use. SIRT2 works mainly in the cytoplasm. Because every sirtuin reaction consumes NAD+, sirtuin activity rises and falls with NAD+ availability. That is the link that connects the cell's energy state to its long-term maintenance: when NAD+ is plentiful, sirtuins can keep genes, mitochondria and DNA in good order; when it falls, that maintenance may slip.

The calorie restriction link

Calorie restriction, the most reliable way to extend lifespan in many laboratory animals, increases NAD+ and sirtuin activity in several tissues. This connection is one of the main reasons NAD+ became central to ageing research, and one reason researchers study whether raising NAD+ can reproduce some of the effects of eating less.

DNA Repair in More Depth

Every cell suffers thousands of DNA lesions a day, from normal metabolism, radiation and chemicals. PARP1, the most active PARP enzyme, detects breaks in DNA within seconds and uses NAD+ to build chains of ADP-ribose that act as a signal flag, recruiting repair proteins. This response is vital, but it is expensive: heavy DNA damage can drain a cell's NAD+, starving sirtuins and energy production. That trade-off between repair and energy is one of the reasons researchers think accumulating DNA damage with age may drive NAD+ decline, as the Sydney skin study suggested.

NAD+ and the Immune System

CD38, one of the main NAD+-consuming enzymes, is abundant on immune cells, and its levels rise with inflammation. Research suggests that the low-grade chronic inflammation that accompanies ageing, sometimes called inflammageing, may increase CD38 activity and so accelerate NAD+ decline. At the same time, immune cells themselves depend on NAD+ to function. This two-way link between NAD+ and the immune system is one of the most active areas of current research.

A Short History of NAD+

Discovered in yeast

NAD+ was discovered in 1906 by the British biochemists Arthur Harden and William John Young, who found that yeast extract needed a small, heat-stable "co-ferment" to ferment sugar. Hans von Euler-Chelpin later worked out much of its chemical nature and shared the 1929 Nobel Prize in Chemistry with Harden.

How it carries hydrogen

In the 1930s, the German biochemist Otto Warburg showed that the nicotinamide part of NAD+ carries hydrogen in metabolic reactions, revealing how the molecule actually works.

The vitamin connection

In 1937, Conrad Elvehjem at the University of Wisconsin showed that nicotinic acid, a form of vitamin B3, cured a pellagra-like disease in dogs. Pellagra, which causes skin inflammation, diarrhoea, dementia and death, was then common where diets relied on maize. Vitamin B3, the raw material for NAD+, eradicated it wherever it was added to diets.

The ageing connection

The modern era of NAD+ research began in 2000, when Imai, Guarente and colleagues showed in Nature that the yeast longevity protein Sir2 is an NAD-dependent enzyme, linking metabolism directly to lifespan (PMID: 10693811). That discovery turned NAD+ from a housekeeping molecule into a central subject of ageing research.

How the Body Makes NAD+

From scratch

Cells can make NAD+ from the amino acid tryptophan through a long pathway, mainly in the liver.

From vitamin B3

Nicotinic acid, one form of vitamin B3, can be converted to NAD+ through what is called the Preiss-Handler pathway.

By recycling: the salvage pathway

Most NAD+ is recycled. When sirtuins, PARPs and CD38 break NAD+ apart, they release nicotinamide. The enzyme NAMPT converts nicotinamide into NMN, nicotinamide mononucleotide, and NMNAT enzymes convert NMN back into NAD+. NAMPT is the rate-limiting step, controlling how fast the loop can run, and its activity follows the body clock and rises with exercise.

The precursors

Molecules that feed these pathways, such as nicotinamide riboside (NR) and NMN, are called NAD+ precursors. They are widely studied as ways of raising NAD+ levels. Our article NAD+ vs NMN explains how they compare.

NAD+ and Ageing: What the Research Shows

Levels fall with age

A 2012 study in PLoS One by Massudi and colleagues in Sydney analysed human skin from people aged 15 to 77 and found that NAD+ declined with age, alongside rising oxidative DNA damage and PARP activity (PMID: 22848760, PMC3407129). Studies in other tissues and in animals have reported similar declines, though the size varies. Our article NAD+ levels by age covers the evidence in detail.

Why it falls

A 2016 study in Cell Metabolism by Camacho-Pereira, Chini and colleagues at the Mayo Clinic identified CD38 as a major driver of age-related NAD+ decline: CD38 rose with age in mice, and mice lacking it were protected from the decline (PMID: 27304511, PMC4911708). Increased consumption by PARPs responding to DNA damage also contributes.

The "Achilles' heel" idea

A 2014 review in Trends in Cell Biology by Imai and Guarente described NAD+ decline as a possible "Achilles' heel" of ageing, summarising research in which restoring NAD+ improved age-associated defects in animal models (PMID: 24786309, PMC4112140). A 2021 review in Nature Reviews Molecular Cell Biology by Covarrubias, Verdin and colleagues set out the full picture of NAD+ metabolism and its roles in ageing (PMID: 33353981, PMC7963035).

Research on Restoring NAD+

In mice

In a 2016 study in Cell Metabolism, Mills, Imai and colleagues gave mice the precursor NMN for a year from middle age and found it mitigated several age-associated changes, including weight gain, reduced energy metabolism, declining physical activity and worsening insulin sensitivity (PMID: 28068222, PMC5668137).

In people

Human research has been smaller and shorter. A 2018 randomised, placebo-controlled trial in Nature Communications found nicotinamide riboside raised NAD+ metabolism in healthy middle-aged and older adults (PMID: 29599478, PMC5876407). A 2021 randomised trial in Science found NMN increased muscle insulin sensitivity in postmenopausal women with prediabetes (PMID: 33888596, PMC8550608). These trials suggest precursors can raise NAD+ metabolism in people, while the broad effects seen in mice have not yet been matched in human studies.

Other approaches

Researchers also study protecting the NAD+ supply. A 2014 study in Nature found that reducing the enzyme NNMT, which removes nicotinamide from the recycling loop, raised NAD+ in fat tissue and protected mice against diet-induced obesity (PMID: 24717514, PMC4107212). The NNMT inhibitor 5-Amino-1MQ is studied for this reason.

Tolerability in Human Studies

Short-term human trials of NAD+ precursors have generally reported good tolerability over the weeks to months studied, and a 2020 safety study of NMN in healthy Japanese men found no significant changes in vital signs and only small laboratory changes within normal ranges (PMID: 31685720). Long-term human data do not yet exist, and researchers have raised theoretical questions that remain open. Our article NAD+ side effects covers this in full.

What the Research Still Needs

Despite two decades of intense study, important questions about NAD+ remain open. Large, long-term human trials are needed to show whether restoring NAD+ changes health outcomes in people, not just NAD+ levels. Standardised measurement methods and reference ranges would make results comparable across studies. Researchers want to know which tissues respond best to which approaches, whether precursors reach the organs that matter most, and what the long-term effects of raising NAD+ above natural levels might be. And the balance between supply and consumption, including the role of inflammation and CD38, is still being worked out. These open questions are what keep NAD+ at the forefront of ageing and metabolic research.

NAD+ Compared With Its Precursors

It helps to be clear about how NAD+ relates to the molecules often discussed alongside it. NAD+ is the working coenzyme. NMN is one step before it in the recycling pathway, and NR is two steps before. Nicotinamide and nicotinic acid are forms of vitamin B3 that feed different pathways. Tryptophan is the starting point for making NAD+ from scratch. In laboratory research, NAD+ is used when researchers want to supply the end product directly or study what happens when it is available outside cells, while precursors are used to study how cells build their own supply. Each tool answers a different question.

Where NAD+ Is Studied

Metabolism

NAD+ research in metabolism focuses on insulin sensitivity, fat metabolism and energy use, including the 2021 NMN muscle trial and the NNMT research in fat tissue.

Mitochondria

The mitochondrial sirtuin SIRT3 depends on NAD+ to keep the energy machinery running efficiently, and NAD+ decline has been linked to mitochondrial dysfunction. See SS-31 vs NAD+.

DNA repair

Because PARPs depend on NAD+, its availability is central to DNA repair research.

Brain

Neurons depend on NAD+ for energy and DNA repair, and its decline has been linked to brain ageing in animal studies.

Muscle and exercise

Exercise increases NAMPT in muscle, and muscle is a key tissue in NAD+ research.

The body clock

NAD+ follows a daily rhythm because NAMPT is controlled by the circadian clock, and sirtuins help regulate the clock in turn.

An Ancient Molecule

NAD+ is found in every form of life that has been studied, from bacteria to plants to people. That universality suggests it is extraordinarily ancient, likely present in the earliest cells. Some scientists have even proposed that its structure, built from nucleotides, is a relic of an early "RNA world" in which RNA-like molecules performed chemistry before proteins took over. Whatever its exact origin, NAD+'s presence across all life shows how fundamental it is to the chemistry of living things.

Common Misconceptions About NAD+

"NAD+ is a vitamin"

NAD+ is made from vitamin B3, but it is not itself a vitamin. The body makes it from several raw materials.

"NAD+ is used up when it makes energy"

In energy production, NAD+ is recycled, switching between NAD+ and NADH. It is consumed, and must be remade, when enzymes such as sirtuins, PARPs and CD38 break it apart.

"Everyone's NAD+ falls at the same rate"

Research shows the decline varies between tissues, between people and between sexes.

"Raising NAD+ reverses ageing"

Restoring NAD+ improved several age-related measures in mice, but human trials have found more modest, specific effects, and there is no evidence that it reverses ageing in people.

"NAD+ is a peptide"

It is a nucleotide coenzyme, not a chain of amino acids.

Designing NAD+ Research

Measure the whole network

NAD+ sits in a network with NADH, NADP+, NADPH, NMN, nicotinamide and their breakdown products. Measuring several of these by mass spectrometry gives a far clearer picture than NAD+ alone.

Measure in the right tissue

Blood levels may not reflect tissue levels, so measuring where an effect is expected matters.

Handle samples quickly

NAD+ and NADH degrade quickly after sampling, so rapid processing is essential.

Control timing and activity

Because NAD+ follows a daily rhythm and responds to exercise, time of day and activity should be controlled.

Link to function

Changes in NAD+ are most meaningful alongside functional measures, such as sirtuin activity, mitochondrial respiration or insulin sensitivity.

How NAD+ Is Measured

Measuring NAD+ accurately is harder than it sounds. NAD+ and NADH interconvert and degrade within minutes of a sample being taken, so researchers freeze or chemically stabilise samples immediately. Enzyme cycling assays can measure total NAD+ and NADH sensitively. Liquid chromatography coupled with mass spectrometry, increasingly the standard, can measure NAD+ alongside its whole network of related molecules, including NMN, NR, nicotinamide and methylated breakdown products. Blood is the easiest sample, but tissue biopsies, such as the skin samples in the Sydney study or muscle biopsies in the NMN trial, give a truer picture of what is happening in specific organs. Commercial blood tests exist, but reference ranges are not standardised.

The Wider NAD+ Toolkit

Researchers now have a range of tools for studying NAD+ biology. NAD+ itself can be supplied directly to cells and enzymes. Precursors such as NMN and NR feed the salvage pathway. Inhibitors of CD38 slow NAD+ consumption, and NNMT inhibitors such as 5-Amino-1MQ protect the nicotinamide supply. Sirtuin activators and PARP inhibitors act on the enzymes that use NAD+. And exercise, calorie restriction and time of day all influence NAD+ naturally. Combining these tools lets researchers separate the effects of supply, recycling and consumption, which is essential for understanding what NAD+ decline actually does.

Why NAD+ Matters for Energy-Hungry Tissues

Tissues that use the most energy, such as heart muscle, skeletal muscle, the brain and the kidneys, are packed with mitochondria and depend heavily on a steady supply of NAD+ to keep their energy production running. They are also the tissues most often affected when mitochondria falter. That is why much NAD+ research focuses on these organs, and why NAD+ is so often studied alongside other mitochondrial research compounds.

The Technical Breakdown

Structure

NAD+ consists of two nucleotides joined through their phosphate groups: nicotinamide mononucleotide and adenosine monophosphate. The nicotinamide ring is where the chemistry happens.

Redox chemistry

The nicotinamide ring accepts a hydride ion, two electrons and a proton, to become NADH, and gives it up again at complex I of the electron transport chain.

How sirtuins use NAD+

Sirtuins cleave NAD+, transferring the acetyl group from a protein onto the ADP-ribose portion and releasing nicotinamide. Nicotinamide itself can inhibit sirtuins at high concentrations, a form of feedback.

Compartments

NAD+ exists in separate pools in the nucleus, cytoplasm and mitochondria, maintained partly independently, which adds complexity to measurement and interpretation.

Extracellular NAD+

Outside cells, NAD+ is broken down by CD38 and CD73 into smaller molecules such as NMN and NR, which cells can take up and rebuild into NAD+.

Why Quality Matters

NAD+ is sensitive to heat, light and moisture. Degraded material contains breakdown products, such as nicotinamide and ADP-ribose, that have their own biological effects and can confound results. Every batch of NAD+ supplied by Crown Peptides comes with a batch-specific certificate of analysis showing HPLC purity and mass spectrometry identity, with lot numbers matching vial labels. Published certificates are on our Lab Reports page, and our guides to testing, reconstitution and storage cover the practical side. Bacteriostatic Water is available alongside.

Related Compounds

Mitochondrial compounds

SS-31 protects the inner mitochondrial membrane, MOTS-c is a mitochondria-encoded signalling peptide, and Methylene Blue can shuttle electrons in the energy chain. See NAD+ vs MOTS-c and Methylene Blue vs NAD+.

Ageing compounds

Epitalon is studied for telomeres; see Epitalon vs NAD+. Glutathione depends on NADPH for recycling.

Metabolic compounds

5-Amino-1MQ protects the NAD+ supply, and L-Carnitine feeds fat into mitochondria. The Metabolic Research Bundle brings metabolic compounds together.

Browse the ageing and cellular research peptides and metabolic research peptides categories, and see best peptides for longevity research.

One Molecule at the Centre of It All

NAD+ began its scientific life as a helper in yeast fermentation and became the cure for pellagra before emerging, a century later, as one of the central molecules of ageing research. It carries the electrons that power every cell and fuels the enzymes that regulate metabolism, repair DNA and respond to stress. Its decline with age, and the question of whether restoring it can change the course of ageing, make it one of the most important and most closely watched subjects in the whole of modern biology.

Explore NAD+ from Crown Peptides, every batch HPLC and mass spectrometry verified and dispatched from the UK.