Nicotinamide adenine dinucleotide (NAD) is a vital coenzyme present in every living cell, essential for energy production, DNA repair, and cellular signalling. Existing in two forms—NAD+ (oxidised) and NADH (reduced)—this molecule plays a fundamental role in human metabolism and cellular function. Derived from vitamin B3 (niacin), NAD levels may decline with age in some tissues, prompting scientific interest in NAD precursor supplementation. Whilst NAD remains an important area of clinical research, particularly regarding metabolic health, it is crucial to distinguish evidence-based applications from unsubstantiated wellness claims. This article examines the science behind NAD, its biological functions, current research evidence, and safety considerations for supplementation.

What Is Nicotinamide Adenine Dinucleotide (NAD)?

Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in every living cell throughout the human body. It exists in two forms: NAD+ (oxidised) and NADH (reduced), which work together in fundamental biochemical processes. This molecule is essential for life, playing a critical role in energy metabolism, DNA repair, and cellular signalling.

NAD is derived from dietary sources of vitamin B3 (niacin), including nicotinic acid, nicotinamide (niacinamide), and nicotinamide riboside. The body synthesises NAD through several pathways, with the salvage pathway being an important route for maintaining cellular NAD levels. Research suggests NAD+ levels tend to decline with age in some tissues, though human data are heterogeneous. This observation has prompted scientific interest in NAD supplementation and its potential applications.

In recent years, NAD has gained attention both in clinical research and the wellness industry. Whilst it remains a legitimate area of scientific investigation, particularly regarding cellular metabolism and metabolic disorders, it is important to distinguish between evidence-based applications and unsubstantiated claims. The molecule's fundamental importance to cellular function has led to exploration of NAD precursors—such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). In Great Britain, nicotinamide riboside chloride has novel food authorisation with specific conditions (for adults, excluding pregnancy and breastfeeding), while NMN is not currently authorised as a novel food. These products are regulated as food supplements by the Food Standards Agency (FSA) and Office for Product Safety and Standards (OPSS), not as medicines.

How NAD Works in the Body

NAD functions primarily as an electron carrier in redox reactions, which are chemical processes involving the transfer of electrons between molecules. In cellular respiration, NAD+ accepts electrons during the breakdown of glucose and other nutrients, becoming NADH. This reduced form then donates electrons to the electron transport chain in mitochondria, the cellular powerhouses, ultimately leading to the production of adenosine triphosphate (ATP)—the body's primary energy currency.

Beyond energy metabolism, NAD+ serves as a substrate for several enzyme families that regulate critical cellular processes:

• Sirtuins: These NAD+-dependent enzymes regulate gene expression, DNA repair, and metabolic pathways. They have been implicated in longevity and stress resistance in various organisms.

• Poly(ADP-ribose) polymerases (PARPs): These enzymes consume NAD+ whilst repairing DNA damage and maintaining genomic stability.

• CD38 and CD157: These enzymes degrade NAD+ and are involved in immune function and cellular signalling.

The balance between NAD+ synthesis and consumption is tightly regulated. When cellular stress increases—through factors such as inflammation, oxidative damage, or metabolic dysfunction—NAD+ consumption accelerates, potentially depleting cellular stores. This depletion may compromise the efficiency of energy production and DNA repair mechanisms.

The salvage pathway recycles nicotinamide back into NAD+, making it an important route for maintaining NAD levels in most tissues. Some preclinical and limited human studies suggest this pathway may become less efficient with age, potentially contributing to changes in tissue NAD+ levels in older adults. However, the evidence in humans remains incomplete. Understanding these mechanisms has informed research into NAD precursor supplementation as a potential strategy to support cellular NAD pools.

Potential Benefits and Current Research Evidence

Research into NAD supplementation, primarily using precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), has explored various potential health applications. However, it is essential to note that most evidence comes from preclinical studies in animal models, with human clinical trials remaining limited in scope and duration.

Metabolic health has been a key area of investigation. Animal studies suggest that boosting NAD+ levels may improve insulin sensitivity, enhance mitochondrial function, and support healthy weight management. Small human trials have shown that NR supplementation can increase NAD+ levels in blood and may improve certain metabolic markers in specific populations, though results have been inconsistent across studies. There is currently insufficient evidence to recommend NAD precursors for treating metabolic disorders, and they are not included in NICE guidance for diabetes management.

In the context of cardiovascular health, preclinical research indicates that NAD+ may support vascular function and blood pressure regulation. However, robust clinical trials demonstrating cardiovascular benefits in humans are lacking. Unlike high-dose nicotinic acid (which is not recommended by NICE for lipid modification), NAD precursors are not part of standard cardiovascular disease management protocols.

Neuroprotection and cognitive function represent another area of interest. Animal models suggest potential benefits for neurodegenerative conditions, but translating these findings to human populations remains challenging. There is no established link between NAD supplementation and prevention or treatment of dementia or other neurological disorders in humans.

Regarding ageing and longevity, whilst NAD+ decline is associated with various age-related changes, evidence that supplementation can extend human lifespan or significantly reverse ageing processes is speculative. The field requires long-term, well-designed clinical trials before definitive conclusions can be drawn about anti-ageing benefits.

It is important to note that there are no authorised health claims for NR or NMN on the Great Britain Nutrition and Health Claims Register, and food supplements cannot claim to treat diseases. Patients considering NAD supplementation should discuss this with their GP, particularly if they have existing health conditions or take prescribed medications.

Safety Considerations and Side Effects of NAD Supplements

NAD precursor supplements, including nicotinamide riboside and nicotinamide mononucleotide, have generally been well-tolerated in clinical trials conducted to date, though long-term safety data remain limited. In Great Britain, these products are regulated as food supplements by the Food Standards Agency (FSA) and Office for Product Safety and Standards (OPSS).

Common side effects reported in clinical studies include:

• Mild gastrointestinal symptoms (nausea, bloating, diarrhoea)

• Flushing or skin warmth (less common than with high-dose nicotinic acid)

• Headache

• Fatigue

These effects are typically mild and resolve with continued use or dose adjustment. However, individuals experiencing persistent or severe symptoms should discontinue use and consult their healthcare provider. Suspected side effects should be reported via the MHRA Yellow Card Scheme.

Important safety considerations include:

Drug interactions: While no well-established clinically relevant interactions have been documented, the evidence is limited. Patients taking prescribed medications should seek medical advice before supplementation.

Pre-existing conditions: Individuals with liver disease or kidney impairment should exercise caution. The theoretical concern regarding active malignancies (based on preclinical research on NAD metabolism) requires further clinical investigation; no formal contraindication has been established.

Pregnancy and breastfeeding: Nicotinamide riboside chloride is not authorised for use during pregnancy or lactation in Great Britain. These supplements should be avoided unless specifically recommended by a healthcare professional.

Quality and regulation: In Great Britain, nicotinamide riboside chloride is an authorised novel food with specific conditions of use (for adults only, excluding pregnancy and breastfeeding), while NMN is not currently authorised as a novel food. Consumers should verify products against GB novel food authorisations and purchase from reputable UK suppliers. Be aware that supplement regulation differs from pharmaceutical standards.

When to seek medical advice: Contact your GP if you experience unusual symptoms after starting NAD supplements, including persistent gastrointestinal disturbance, unexplained fatigue, or any concerning changes in health status. Patients should inform healthcare providers about all supplements taken, as this information is relevant for clinical decision-making and potential investigation of symptoms.

Frequently Asked Questions