Nicotinamide adenine dinucleotide (NAD+) is a vital coenzyme present in every living cell, essential for energy production and cellular metabolism. Interest in the benefits of NAD+ has grown significantly as research reveals that NAD+ levels naturally decline with age, potentially affecting mitochondrial function and overall cellular health. NAD+ precursor supplements, particularly nicotinamide riboside (NR), have emerged as potential interventions to support cellular function. However, whilst animal studies show promise, human clinical evidence remains limited. This article examines the current evidence for NAD+ supplementation, safety considerations, and UK regulatory guidance to help healthcare professionals and patients make informed decisions.

What Is NAD+ and How Does It Work in the Body?

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in every living cell, playing a fundamental role in cellular metabolism and energy production. This molecule exists in two forms: NAD+ (oxidised) and NADH (reduced), which work together in redox reactions essential for life. NAD+ is particularly crucial for converting nutrients from food into adenosine triphosphate (ATP), the primary energy currency of cells.

The body synthesises NAD+ through several pathways: the de novo pathway from the amino acid tryptophan and the salvage pathway primarily from dietary niacin (vitamin B3) and nicotinamide. Nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are intermediates that occur in small amounts in some foods and can also contribute to NAD+ production. These precursors are converted through enzymatic processes into NAD+, which then participates in hundreds of metabolic reactions.

NAD+ levels naturally decline with age, a phenomenon observed across multiple tissues and organs. Research suggests this decline may contribute to age-related cellular dysfunction and metabolic changes. By the time individuals reach middle age, NAD+ concentrations can be significantly lower than in youth. This reduction affects mitochondrial function, the cellular powerhouses responsible for energy production, potentially impacting overall cellular health and resilience.

Beyond energy metabolism, NAD+ serves as a substrate for several important enzyme families, including poly(ADP-ribose) polymerases (PARPs), which are involved in DNA repair, and CD38, an enzyme that regulates immune function and cellular signalling. The consumption of NAD+ by these enzymes, alongside changes in salvage pathway efficiency, contributes to age-related NAD+ decline. Understanding these mechanisms has driven interest in NAD+ supplementation as a potential strategy to support cellular function, though the clinical significance of supplementation remains an active area of research.

Evidence-Based Benefits of NAD+ Supplementation

Current research into NAD+ supplementation has primarily focused on precursor molecules such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which are converted to NAD+ in the body. Whilst animal studies have shown promising results, human clinical evidence remains limited and preliminary. It is important to note that many claimed benefits require further robust clinical investigation before definitive conclusions can be drawn.

Cellular energy and mitochondrial function represent the most biologically plausible area of benefit. Small human trials have demonstrated that NR supplementation can increase NAD+ levels in blood cells and peripheral blood mononuclear cells (PBMCs), with more variable evidence for increases in skeletal muscle. A 2018 study published in Nature Communications found that NR supplementation increased NAD+ levels in healthy older adults, but functional benefits were modest.

Metabolic health has been investigated in several trials. Some research indicates that NAD+ precursors may influence insulin sensitivity and lipid metabolism in specific populations, particularly those with metabolic syndrome or obesity. However, results have been inconsistent, and NICE does not currently recommend NAD+ supplementation for diabetes or metabolic conditions. Standard lifestyle interventions—including diet, exercise, and evidence-based medications—remain the cornerstone of metabolic disease management as outlined in NICE guideline NG28 for type 2 diabetes.

Cardiovascular and neuroprotective effects have been suggested by preclinical research, but human evidence is extremely limited. Whilst animal models have shown potential benefits for vascular health and cognitive function, there is no established link between NAD+ supplementation and prevention of cardiovascular disease or dementia in humans. Claims regarding anti-ageing effects, whilst popular in wellness circles, lack robust clinical validation. Under GB Nutrition and Health Claims regulations, no health claims are authorised for NR or NMN supplements. Patients concerned about cardiovascular risk should focus on established preventive measures including blood pressure control, cholesterol management, smoking cessation, and regular physical activity, as recommended by NICE guideline NG238.

Safety Considerations and Potential Side Effects of NAD+

NAD+ precursor supplements are not currently regulated as medicines by the MHRA. In Great Britain, nicotinamide riboside (NR) chloride is authorised as a novel food supplement with specific conditions, while nicotinamide mononucleotide (NMN) is not authorised as a novel food and should not be marketed as a food supplement in the UK.

Common side effects reported in clinical trials of nicotinamide riboside have been mild and include:

• Nausea and gastrointestinal discomfort

• Headache

• Fatigue or dizziness

• Mild digestive upset including bloating or diarrhoea

Unlike nicotinic acid (a form of niacin), NR and niacinamide typically do not cause flushing. These effects are generally dose-dependent and often resolve with continued use or dose reduction.

Important safety considerations include the UK regulatory status. For nicotinamide riboside chloride, the Food Standards Agency (FSA) has authorised a maximum daily intake of 300 mg for adults only. It is not authorised for use during pregnancy or breastfeeding, or for people under 18 years of age. NMN is not authorised as a novel food in Great Britain and should be avoided.

Patients taking medications that affect blood pressure or glucose metabolism should consult their GP before starting NR supplementation, as some studies have reported modest effects on these parameters. There is currently insufficient evidence regarding safety in pregnancy and breastfeeding, and these supplements should be avoided in these populations. Similarly, safety data in children and adolescents is lacking. Individuals with existing liver or kidney disease should exercise caution, as these organs are involved in NAD+ metabolism.

When to seek medical advice: Patients should contact their GP if they experience persistent side effects or unexplained symptoms after starting supplementation. It is essential to inform healthcare providers about all supplements being taken. Suspected adverse reactions should be reported through the MHRA Yellow Card Scheme. Supplements should never replace prescribed medications without medical supervision.

How to Use NAD+ Supplements: Dosage and Forms

NAD+ supplements are available in several forms, each with different bioavailability and evidence bases. The most commonly studied forms include nicotinamide riboside (NR) and nicotinamide (niacinamide). Direct NAD+ supplementation is less common due to poor oral bioavailability, as the molecule is too large to be efficiently absorbed intact through the digestive system.

Nicotinamide riboside (NR) chloride is the most extensively researched precursor in human trials. In the UK, NR chloride is an authorised novel food with specific conditions of use. The maximum permitted daily dose is 300 mg for adults only. It is not authorised for use during pregnancy or breastfeeding, or for people under 18 years of age. NR is available in capsule form and has demonstrated the ability to increase blood NAD+ levels in clinical trials.

Nicotinamide mononucleotide (NMN) is not authorised as a novel food in Great Britain and should not be marketed or purchased as a food supplement in the UK. Consumers should be aware that NMN products sold online may not comply with UK regulations.

Practical guidance for use of authorised NR supplements includes:

• Do not exceed the UK authorised maximum dose of 300 mg daily for adults

• Take with food to minimise gastrointestinal side effects

• Maintain consistency in timing (morning administration is common)

• Purchase from reputable suppliers that comply with UK regulations

• Check product labels for compliance with novel food authorisation conditions

It is important to emphasise that there are no authorised health claims for NR supplements in Great Britain, and these products should not be considered substitutes for evidence-based medical treatments. Under GB Nutrition and Health Claims regulations, supplements cannot claim to prevent, treat or cure diseases, or make anti-ageing claims. Patients considering NR supplementation should discuss this with their GP, particularly if they have existing health conditions or take regular medications. A balanced diet rich in B vitamins, regular physical activity, and adequate sleep remain the foundation of cellular health and should not be overlooked in favour of supplementation.

Frequently Asked Questions