Nicotinamide adenine dinucleotide (NAD) supplements have gained considerable attention for their potential role in supporting cellular energy and healthy ageing. NAD+ is a vital coenzyme involved in hundreds of metabolic processes, and its levels naturally decline with age. However, NAD supplements do not contain NAD+ itself; instead, they provide precursors such as nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), nicotinamide, or nicotinic acid, which the body converts into NAD+. Whilst the biochemistry is well-established, clinical evidence for meaningful health benefits in humans remains limited. This article examines the types of NAD supplements available in the UK, key selection factors, current evidence, and important safety considerations.

What Are NAD Supplements and How Do They Work?

Nicotinamide adenine dinucleotide (NAD) is a coenzyme found in every living cell, playing a crucial role in energy metabolism and cellular function. NAD exists in two forms: NAD+ (oxidised) and NADH (reduced). As we age, cellular NAD+ levels naturally decline, which has led to considerable interest in supplementation to restore these levels.

NAD supplements do not typically contain NAD+ itself, as this molecule is poorly absorbed when taken orally and rapidly degraded in the digestive system. Although some products market oral or sublingual NAD+, their absorption remains uncertain. Instead, most supplements contain NAD precursors—compounds that the body can convert into NAD+ through specific metabolic pathways. The most common precursors include nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), nicotinamide (also called niacinamide), and nicotinic acid (niacin).

Once absorbed, these precursors enter cellular biosynthetic pathways. Nicotinamide riboside, for example, is phosphorylated to NMN, which is then converted to NAD+ through the enzyme nicotinamide mononucleotide adenylyltransferase (NMNAT). This newly synthesised NAD+ can then participate in hundreds of enzymatic reactions, particularly those involving sirtuins and poly(ADP-ribose) polymerases (PARPs), which are implicated in DNA repair, gene expression, and cellular stress responses.

The theoretical rationale for NAD supplementation centres on supporting mitochondrial function, enhancing cellular energy production, and potentially slowing aspects of cellular ageing. However, it is important to note that whilst the biochemistry is well established, the clinical benefits in humans remain an active area of research, and NAD supplements are not currently recognised as medicines by the MHRA for treating specific conditions. It's worth noting that high-dose nicotinic acid is a licensed medicine in the UK and is not recommended by NICE for lipid modification.

Types of NAD Supplements Available in the UK

Several NAD precursor supplements are available in the UK market, each with distinct characteristics and proposed advantages. Understanding these differences can help inform selection, though it should be noted that these products are regulated as food supplements rather than medicines.

Nicotinamide riboside (NR) is one of the most extensively studied NAD precursors. It is a form of vitamin B3 that has been shown to raise NAD+ levels in human studies. In Great Britain, nicotinamide riboside chloride is an authorised novel food with a typical maximum adult intake of around 300 mg per day and is not authorised for use during pregnancy or lactation. Commercial formulations should adhere to these regulatory limits.

Nicotinamide mononucleotide (NMN) is another precursor that sits one step closer to NAD+ in the biosynthetic pathway. Whilst NMN has shown promise in animal research, human clinical data remain limited, and its bioavailability in humans is still uncertain. Importantly, NMN is not currently authorised as a novel food in Great Britain or the EU, meaning it should not be sold as a food supplement unless/until it receives authorisation.

Nicotinamide (niacinamide) is a well-established form of vitamin B3 that has been used for decades in dermatology and other medical contexts. It raises NAD+ levels through the salvage pathway and does not cause the flushing associated with nicotinic acid. The UK Expert Group on Vitamins and Minerals (EVM) guidance level for nicotinamide is 500 mg per day; higher intakes should only be taken under medical supervision.

Nicotinic acid (niacin) is the original form of vitamin B3. At high doses (gram-level), it is a licensed medicine in the UK and is not recommended by NICE for lipid management due to side effect concerns. It commonly causes uncomfortable flushing due to prostaglandin release, which limits its acceptability. Modified-release formulations exist but may carry hepatotoxicity risks at higher doses.

Many UK products also contain combination formulations that include NAD precursors alongside other compounds such as resveratrol, pterostilbene, or quercetin, based on theories of synergistic effects, though robust clinical evidence for such combinations is generally lacking.

Choosing the Best NAD Supplement: Key Factors to Consider

Selecting an appropriate NAD supplement requires careful consideration of several factors, as the UK market contains numerous products with varying quality, formulation, and evidence bases.

Quality and manufacturing standards should be a primary consideration. Look for products manufactured to appropriate food safety standards such as HACCP-based systems (e.g., BRCGS, ISO 22000). Third-party testing certificates, when available, provide additional assurance regarding the actual content and absence of contaminants. Athletes should consider products with Informed-Sport certification to minimise contamination risks. Reputable manufacturers should be transparent about their sourcing and testing procedures.

Bioavailability and formulation vary between products. Some manufacturers use proprietary formulations claiming enhanced absorption, though independent verification of such claims is often limited. The form of the precursor matters: NR has demonstrated bioavailability in humans, whilst NMN's human bioavailability remains less well-established despite promising animal data. Standard nicotinamide is well-absorbed but may be less efficient at raising NAD+ levels in certain tissues.

Dosage and cost-effectiveness require practical consideration. For NR, remember that in Great Britain, the authorised intake is typically around 300 mg per day for adults. Higher doses do not necessarily confer proportionally greater benefits, and cost per milligram of active ingredient varies considerably across brands. Calculate the monthly cost based on the recommended dosage to make meaningful comparisons.

Evidence base for the specific product is important, though challenging to assess. Whilst some branded formulations have been used in published clinical trials, many products contain the same active ingredients without direct clinical testing. Be cautious of marketing claims that extrapolate from animal studies or use vague terminology like "anti-ageing" without substantiation.

Individual health status and medications must be considered. Those with existing medical conditions, particularly liver disease, diabetes, gout or hyperuricaemia, or cardiovascular conditions, should consult their GP before commencing NAD supplementation. Similarly, individuals taking multiple medications should seek professional advice regarding potential interactions.

Finally, realistic expectations are essential. NAD supplements are not medicines and should not be viewed as treatments for specific diseases. There is no official link established between NAD supplementation and prevention or cure of age-related conditions, despite promising preliminary research.

Evidence for NAD Supplement Benefits and Effectiveness

The evidence base for NAD supplementation in humans is evolving but remains limited compared to the extensive preclinical research. It is crucial to distinguish between well-established biochemical effects and clinically meaningful health outcomes.

Biochemical efficacy is relatively well-demonstrated. Multiple human studies have confirmed that oral NR and NMN supplementation can increase blood NAD+ levels and, in some tissues, intracellular NAD+ concentrations. Human trials have found that NR supplementation at doses within the UK-authorised intake (around 300 mg daily) can elevate NAD+ biomarkers in blood, though tissue-specific effects varied. This biochemical change confirms that these supplements function as intended at a molecular level.

Regarding clinical benefits, the evidence is more preliminary. Small human trials have investigated various outcomes:

• Metabolic health: Some studies suggest modest improvements in insulin sensitivity in overweight or obese individuals (Dollerup et al., 2018), though results are inconsistent. A 2022 trial found no significant metabolic benefits in healthy adults taking NR.

• Cardiovascular function: Limited evidence suggests potential improvements in blood pressure and arterial stiffness in middle-aged adults (Martens et al., 2018), but larger trials are needed for confirmation.

• Cognitive function: Despite promising animal data, human evidence for cognitive benefits remains sparse and inconclusive.

• Exercise performance: Results are mixed, with some studies showing no enhancement in athletic performance or recovery (Elhassan et al., 2019).

• Ageing biomarkers: Whilst some trials report changes in markers associated with cellular ageing, there is no official link established between NAD supplementation and longevity or prevention of age-related diseases in humans.

The quality of existing evidence presents limitations. Most human trials are small (fewer than 100 participants), short-term (12 weeks or less), and often funded by supplement manufacturers. Many studies have used doses exceeding the UK-authorised intake for NR, so results may not generalise to UK-permitted levels. Long-term safety and efficacy data spanning years are notably absent. NICE does not currently provide guidance on NAD supplementation, as it is not recognised as a therapeutic intervention for any specific condition.

Patients should understand that whilst the biological rationale is sound and preliminary human data are encouraging, definitive evidence for meaningful health benefits remains to be established through larger, independent, long-term clinical trials.

Safety, Side Effects and Interactions of NAD Supplements

NAD precursor supplements are generally well-tolerated in short-term studies, but comprehensive long-term safety data in humans are limited. Understanding potential adverse effects and interactions is essential for informed decision-making.

Common side effects reported in clinical trials are typically mild and include:

• Nausea or gastrointestinal discomfort (particularly at higher doses)

• Flushing and itching (primarily with nicotinic acid; rare with NR or nicotinamide)

• Headache

• Fatigue or dizziness

• Skin reactions (uncommon)

These effects are generally dose-dependent and often resolve with continued use or dose reduction. In published trials, discontinuation rates due to adverse effects are low, suggesting acceptable tolerability for most individuals.

Theoretical concerns warrant consideration despite limited human evidence. NAD+ plays complex roles in cellular metabolism, and chronic elevation could theoretically affect:

• Cancer risk: NAD+ supports PARP enzymes involved in DNA repair, but also fuels rapidly dividing cells. The long-term oncological implications of sustained NAD+ elevation remain unknown.

• Methylation pathways: High-dose nicotinamide may affect methyl group availability, potentially impacting epigenetic regulation, though clinical significance is uncertain.

Drug interactions require attention. NAD precursors may interact with:

• Diabetes medications: Nicotinic acid (niacin) can worsen glycaemic control, potentially interfering with diabetes management.

• Blood pressure medications: Some evidence suggests NAD precursors may lower blood pressure, potentially enhancing antihypertensive effects.

• Statins: Nicotinic acid can increase the risk of myopathy (muscle damage) when combined with statins.

Contraindications and precautions include:

• Pregnancy and breastfeeding: Safety data are insufficient; avoidance is prudent. NR is specifically not authorised for use during pregnancy or lactation in the UK.

• Liver disease: High-dose niacin can cause hepatotoxicity; this risk is heightened with alcohol or hepatotoxic drugs. Caution is advised with all NAD precursors.

• Gout or hyperuricaemia: Niacin can raise uric acid levels and potentially trigger gout attacks.

• Active malignancy: Theoretical concerns warrant discussion with oncology specialists.

• Children and adolescents: Use should be avoided due to limited safety data.

When to seek medical advice: Contact your GP if you experience persistent gastrointestinal symptoms, unexplained fatigue, jaundice, or any concerning symptoms after starting NAD supplements. Individuals with pre-existing medical conditions should consult their healthcare provider before commencing supplementation.

If you suspect you have experienced a side effect from an NAD supplement, report it to the MHRA through the Yellow Card Scheme (yellowcard.mhra.gov.uk).

NAD supplements should complement, not replace, evidence-based medical treatments and healthy lifestyle measures including balanced nutrition, regular physical activity, and adequate sleep.

Frequently Asked Questions