Nicotinamide adenine dinucleotide (NAD) supplementation has gained considerable attention as a potential anti-ageing and metabolic health intervention. NAD+ is a vital coenzyme involved in cellular energy production, DNA repair, and metabolic regulation, with levels declining naturally with age. This has prompted interest in NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) as supplements. Whilst animal studies show promise, human clinical evidence remains limited and preliminary. This article examines the scientific evidence, potential benefits, safety considerations, and UK regulatory status to help you understand whether NAD supplementation truly delivers meaningful health benefits.

What Is NAD and How Does It Function 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 converting nutrients into cellular energy through processes such as glycolysis and the citric acid cycle.

NAD+ serves multiple critical functions beyond energy metabolism. It acts as a substrate for several enzyme families, including sirtuins, poly(ADP-ribose) polymerases (PARPs), and CD38/CD157. Sirtuins regulate gene expression, DNA repair, and cellular stress responses, whilst PARPs are involved in DNA damage repair and genomic stability. These enzymes consume NAD+ to perform their functions, making adequate NAD+ levels essential for cellular health and various cellular processes linked with ageing.

Research suggests NAD+ levels naturally decline with age in various tissues, with studies showing significant reductions between youth and middle age, though the extent varies by tissue type. This decline has been associated with mitochondrial dysfunction, reduced cellular repair capacity, and age-related metabolic changes. The decrease occurs partly because NAD+-consuming enzymes become more active with age, particularly in response to accumulated cellular damage, whilst NAD+ biosynthesis pathways may become less efficient.

The body synthesises NAD+ through three main pathways: the de novo pathway from tryptophan, the Preiss-Handler pathway from nicotinic acid, and the salvage pathway from nicotinamide. The salvage pathway, which recycles nicotinamide back into NAD+, is the predominant route in most tissues and represents the primary target for NAD+ supplementation strategies.

Scientific Evidence: Does NAD Supplementation Really Work?

The scientific evidence for NAD supplementation presents a complex picture, with preclinical studies showing promise but human clinical data remaining limited. Most compelling evidence comes from animal models, where NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) have demonstrated the ability to raise tissue NAD+ levels and improve various metabolic parameters.

In rodent studies, NAD+ precursor supplementation has been associated with improved mitochondrial function, enhanced insulin sensitivity, increased exercise endurance, and protection against age-related metabolic decline. These findings have generated considerable interest in translating these benefits to humans. However, it is crucial to recognise that animal studies do not always predict human outcomes, and the doses used in research often exceed those practical for human consumption when adjusted for body weight.

Human clinical trials, whilst growing in number, remain relatively small-scale and short-term. Studies have confirmed that oral supplementation with NR and NMN can increase blood NAD+ levels in humans, with doses typically ranging from 250mg to 1000mg daily. However, it's important to note that increases in blood NAD+ may not necessarily reflect tissue-specific changes or translate to clinical benefits.

Some small trials have reported specific outcomes: NMN supplementation improved muscle insulin sensitivity in prediabetic women in one study (Yoshino et al., 2021), while NR trials have shown inconsistent metabolic effects. Research on muscle function in older adults has produced mixed results, with some studies showing no improvement in muscle mitochondrial function despite raising NAD+ levels (Elhassan et al., 2019).

Systematic reviews of human trials indicate that whilst NAD+ precursors appear safe and can raise NAD+ levels, evidence for clinically meaningful health benefits remains preliminary. Key limitations of current human research include small sample sizes (often fewer than 50 participants), short study durations (typically 6-12 weeks), heterogeneous outcome measures, and a lack of long-term safety data. Additionally, most studies have been conducted in specific populations, such as older adults or those with metabolic dysfunction, making it difficult to generalise findings to healthy individuals seeking preventative benefits.

Potential Benefits and Limitations of NAD Therapy

Proponents of NAD supplementation cite several potential benefits based on its cellular functions, though the strength of evidence varies considerably across different claims. Metabolic health represents one area with emerging support, as some small human trials have demonstrated improvements in insulin sensitivity in individuals with obesity or prediabetes, particularly with NMN supplementation. The theoretical mechanism involves NAD+'s role in mitochondrial function and sirtuin activation, which regulate glucose and fat metabolism.

Cognitive function and neuroprotection are frequently mentioned benefits, supported by preclinical evidence showing NAD+ precursors may protect neurons from damage and support brain energy metabolism. However, human evidence remains sparse, with most claims extrapolated from animal studies. Similarly, anti-ageing effects are often promoted based on NAD+'s role in DNA repair and cellular maintenance, but there is no established evidence linking NAD supplementation to extended human lifespan or reversal of ageing processes.

Other proposed benefits include:

• Enhanced exercise performance and recovery – limited human data with mixed results

• Cardiovascular health – primarily theoretical, based on vascular function studies in animals with minimal human evidence

• Immune function support – early-stage research with no robust clinical evidence

• Improved sleep quality – anecdotal reports lacking rigorous scientific validation

Significant limitations must be considered when evaluating NAD therapy. Firstly, bioavailability varies between different NAD+ precursors and delivery methods, with oral supplements potentially degraded in the digestive system before reaching target tissues. Intravenous NAD+ infusions, whilst offered in some private clinics, are unlicensed treatments in the UK with specific risks including infection, phlebitis, electrolyte disturbances, and hypersensitivity reactions. They lack robust safety and efficacy data and are not endorsed by the NHS or NICE.

Secondly, the optimal dosing, timing, and duration of supplementation remain unclear. Thirdly, individual responses appear highly variable, likely influenced by baseline NAD+ status, age, metabolic health, and genetic factors. Finally, the long-term effects of artificially elevating NAD+ levels are unknown, raising questions about potential unintended consequences of chronic supplementation.

It's important to note that in Great Britain, nicotinamide riboside chloride is an authorised novel food ingredient with specified conditions of use, while NMN is not currently authorised as a novel food and should not be marketed as a food supplement.

Safety Considerations and Side Effects of NAD

Current evidence suggests that NAD+ precursors are generally well-tolerated at doses studied in clinical trials. Nicotinamide riboside has been studied at doses up to 1000mg daily for several weeks, while NMN has been tested at similar doses in shorter-term studies. However, comprehensive long-term safety data (beyond one year) are lacking, and post-marketing surveillance is limited given these supplements' relatively recent popularity.

Commonly reported side effects are typically mild and may include:

• Nausea or gastrointestinal discomfort, particularly at higher doses

• Headache

• Fatigue or changes in energy levels

• Mild dizziness

It's important to distinguish between different forms of vitamin B3. Nicotinic acid (niacin) commonly causes flushing and skin warmth, but this is not typically seen with nicotinamide, NR, or NMN. These effects are generally dose-dependent and often resolve with continued use or dose reduction. Taking supplements with food may reduce gastrointestinal symptoms.

Important safety considerations include potential drug interactions. While specific interactions with NR and NMN are not well-established due to limited clinical data, high-dose nicotinic acid (a different form of vitamin B3) can worsen glycaemic control, raise uric acid levels, and increase the risk of myopathy when taken with statins or fibrates. Individuals taking any medications should consult their GP or pharmacist before starting NAD supplementation.

There is theoretical concern that boosting NAD+ levels could potentially support the growth of existing cancer cells, as rapidly dividing cells have high energy demands, though this remains speculative without clinical evidence.

Specific populations should exercise particular caution. Pregnant and breastfeeding women should avoid NAD supplementation due to absent safety data. Individuals with liver or kidney disease should seek medical advice, as these organs play crucial roles in NAD metabolism and clearance. Those with active malignancies should discuss supplementation with their oncologist.

When to contact your GP: Seek medical advice if you experience persistent side effects, unusual symptoms after starting NAD supplementation, or if you have underlying health conditions. Any new supplements should be discussed with your healthcare provider, particularly if you take prescription medications or have chronic health conditions. Report any suspected adverse reactions to the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk).

NHS and NICE Guidance on NAD Supplementation

Currently, neither NICE nor the NHS provides specific guidance on NAD supplementation, reflecting the limited clinical evidence base and the classification of NAD+ precursors as food supplements rather than medicines in the UK. These products are not routinely prescribed on the NHS, and patients seeking NAD therapy typically purchase supplements privately or access intravenous treatments through private clinics.

The Medicines and Healthcare products Regulatory Agency (MHRA) regulates NAD-containing products based on their classification. Most oral NAD+ precursors are marketed as food supplements and therefore fall outside the medicines regulatory framework, provided they make no medicinal claims. This means they are not subject to the same rigorous safety and efficacy testing required for licensed medicines.

Regarding regulatory status in Great Britain, nicotinamide riboside chloride is an authorised novel food ingredient with specified conditions of use, while nicotinamide mononucleotide (NMN) is not currently authorised as a novel food and should not be marketed as a food supplement. Intravenous NAD+ is an unlicensed treatment in the UK, not supported by NHS or NICE guidance.

Consumers should be aware that supplement quality and purity can vary between manufacturers, and products are not routinely tested by regulatory authorities. Additionally, under the GB Nutrition and Health Claims Register, supplements cannot make unauthorised health claims about their effects.

The NHS approach to nutritional supplementation generally emphasises obtaining nutrients through a balanced diet rather than supplements, except where specific deficiencies are identified or certain populations have increased requirements (such as vitamin D supplementation or folic acid in pregnancy). This evidence-based, conservative approach reflects the principle that supplementation should address identified needs rather than speculative benefits.

Patient advice from an NHS perspective would likely include:

• Prioritising evidence-based lifestyle interventions (diet, exercise, sleep) for metabolic health and healthy ageing

• Discussing any supplement use with your GP, particularly if you have health conditions or take medications

• Being cautious of exaggerated marketing claims lacking robust clinical evidence

• Ensuring any supplements purchased are from reputable manufacturers with quality assurance

• Recognising that private treatments, including intravenous NAD therapy, are not endorsed by NHS clinical guidelines

For individuals interested in optimising NAD+ levels through dietary means, foods rich in NAD+ precursors include dairy products, fish, mushrooms, green vegetables, and whole grains. However, there is no established evidence linking dietary intake of these foods to clinically significant increases in tissue NAD+ levels. Patients seeking personalised advice about supplementation should consult their GP or a registered dietitian who can assess individual circumstances and provide evidence-based recommendations.

Frequently Asked Questions