NAD+ (nicotinamide adenine dinucleotide), nicotinamide riboside and resveratrol have attracted considerable attention as potential cellular health supplements. NAD+ is a vital coenzyme involved in energy metabolism and DNA repair, with levels declining naturally with age. Nicotinamide riboside (NR), a form of vitamin B3, serves as a precursor that may increase NAD+ levels, whilst resveratrol—a polyphenol found in red grapes—has been studied for its antioxidant properties. Both are regulated as novel foods in the UK with specific authorised conditions. However, whilst the biological mechanisms are scientifically interesting, clinical evidence for meaningful health benefits in humans remains limited and preliminary.

What Are NAD+, Nicotinamide Riboside and Resveratrol?

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme found in every living cell, playing a fundamental role in energy metabolism and cellular repair processes. NAD+ levels naturally decline with age, which has led to considerable scientific interest in strategies to maintain or restore cellular NAD+ concentrations. This molecule is essential for mitochondrial function, DNA repair mechanisms, and the activity of enzymes called sirtuins, which regulate cellular health and longevity pathways.

Nicotinamide riboside (NR) is a form of vitamin B3 that serves as a precursor to NAD+. When consumed, NR is converted through enzymatic pathways into NAD+ within cells. While laboratory studies suggest NR may increase NAD+ levels, comparative human studies with other forms of vitamin B3 (nicotinic acid or nicotinamide) remain limited. In the UK, nicotinamide riboside chloride is an authorised novel food with specific conditions, including a maximum daily intake of 300mg for adults and is not recommended during pregnancy or breastfeeding.

Resveratrol is a polyphenolic compound found naturally in red grapes, berries, and certain plants. It belongs to a class of compounds called stilbenes and has been studied for its potential antioxidant properties and ability to influence sirtuin activity. High-purity trans-resveratrol is also regulated as a novel food in Great Britain with specific authorised conditions. Both compounds are classified as food supplements in the UK, not medicines, and no authorised health claims exist specifically for 'NAD+ boosting' or anti-ageing effects. Only general vitamin B3 (niacin) claims may be made where products meet specific criteria.

How Nicotinamide Riboside and Resveratrol Work Together

The theoretical rationale for combining nicotinamide riboside with resveratrol centres on their complementary mechanisms at the cellular level. NR increases the availability of NAD+, which serves as an essential cofactor for sirtuin enzymes (particularly SIRT1, SIRT3, and SIRT6). These sirtuins regulate numerous cellular processes including mitochondrial biogenesis, oxidative stress responses, and DNA repair. Without adequate NAD+, sirtuin activity may be compromised, potentially affecting cellular resilience and metabolic function.

Resveratrol has been proposed to influence sirtuin activity, particularly SIRT1, though the precise mechanism in humans remains unclear and debated. The effects of resveratrol appear to be pleiotropic, potentially involving multiple pathways including AMP-activated protein kinase (AMPK). The combination hypothesis suggests that by simultaneously increasing NAD+ availability (through NR) and potentially influencing sirtuin-related pathways (through resveratrol), there might be beneficial effects on cellular metabolism and stress resistance.

However, it is important to emphasise that whilst this mechanism is biologically plausible and supported by preclinical research in cell cultures and animal models, there is limited high-quality clinical evidence demonstrating meaningful health benefits in humans from this combination. Most mechanistic studies have been conducted in laboratory settings, and translating these findings to clinical outcomes requires rigorous human trials. No UK health authority or body recommends this combination for any health condition.

Patients considering these supplements should understand that whilst the biological mechanisms are scientifically interesting, the clinical significance for human health outcomes remains uncertain and requires further investigation through well-designed randomised controlled trials.

Evidence for NAD+ Boosting Supplements in the UK

The evidence base for NAD+ precursors and resveratrol in humans is evolving but remains limited in scope and quality. Small-scale clinical trials have demonstrated that nicotinamide riboside supplementation can increase blood NAD+ levels in healthy adults, confirming its bioavailability. Studies published in peer-reviewed journals have shown dose-dependent increases in NAD+ concentrations in blood, though effects in specific tissues like skeletal muscle have shown inconsistent results.

However, demonstrating increased blood NAD+ levels does not automatically translate to clinical health benefits. Research investigating outcomes such as improved metabolic markers, enhanced physical performance, or cognitive function has produced mixed results. Some small trials have suggested potential benefits for blood pressure, insulin sensitivity, or markers of inflammation in specific populations, but these findings require replication in larger, more diverse cohorts before firm conclusions can be drawn.

Resveratrol research in humans has similarly shown inconsistent results. Whilst some studies report improvements in cardiovascular risk markers or glucose metabolism, others have found no significant effects. The bioavailability of resveratrol is relatively poor, with rapid metabolism limiting the amount that reaches target tissues, which may explain some of the disappointing clinical outcomes despite promising preclinical data.

In the UK context, neither the NHS nor NICE currently recommends NAD+ precursors or resveratrol for any specific medical condition. These supplements are not prescribed on the NHS and are not included in clinical guidelines for disease prevention or treatment. No authorised health claims exist in the UK for 'NAD+ boosting' or anti-ageing effects of these supplements. Only general vitamin B3 (niacin) claims may be made where products meet specific criteria.

Healthcare professionals should counsel patients that whilst these supplements are generally considered safe for healthy adults when used according to authorised conditions, the evidence for meaningful health benefits remains preliminary. Patients with specific health conditions should not substitute evidence-based treatments with unproven supplements, and any decision to use these products should be discussed with their GP, particularly if they are taking prescribed medications.

Safety, Side Effects and Regulatory Status

Nicotinamide riboside is generally well-tolerated in clinical trials at doses within authorised limits. Reported adverse effects are typically mild and may include:

• Nausea or gastrointestinal discomfort

• Headache

• Fatigue or dizziness

• Flushing (less common than with nicotinic acid)

• Itching or skin reactions (rare)

Some studies have reported that NR supplementation may increase homocysteine levels in some individuals, which could theoretically affect cardiovascular risk. People with elevated homocysteine or cardiovascular concerns should discuss this with their healthcare provider before use.

Resveratrol supplements are also generally considered safe for short-term use within authorised limits, with most studies reporting minimal side effects. Potential adverse effects include:

• Digestive upset or diarrhoea

• Nausea

• Abdominal discomfort

Important safety considerations include potential drug interactions. Resveratrol may interact with anticoagulants such as warfarin, antiplatelet medications, and drugs metabolised by CYP2C9 or CYP3A4 enzymes. This could potentially increase bleeding risk or alter drug levels. Patients should consider stopping resveratrol 1-2 weeks before scheduled surgery and should always inform their healthcare providers about supplement use. Patients taking prescribed medications should consult their GP or pharmacist before starting these supplements.

Regulatory status in the UK: Nicotinamide riboside chloride and certain high-purity trans-resveratrol products are authorised novel foods in Great Britain, with specific conditions including maximum daily intake limits (e.g., 300mg/day for NR chloride). As novel foods, they have undergone pre-market safety assessment. These products are not recommended during pregnancy or breastfeeding unless specifically advised by a healthcare professional. While regulated as food supplements, they must comply with food safety regulations and cannot make unauthorised health claims.

Patients should be aware that food supplements are not subject to the same rigorous testing as medicines, and quality can vary between manufacturers. There is no official link established between these supplements and treatment or prevention of specific diseases. Any unusual symptoms following supplement use should prompt discontinuation and consultation with a healthcare professional. Suspected adverse reactions can be reported through the MHRA Yellow Card Scheme.

Dosage Guidance and Choosing Quality Supplements

There are no official UK therapeutic dosage recommendations for nicotinamide riboside or resveratrol, as these are not recognised medicines. However, important regulatory limits do exist:

Nicotinamide riboside: In Great Britain, nicotinamide riboside chloride is authorised as a novel food with a maximum daily intake of 300mg for adults. This is the legal limit regardless of what doses may have been used in research settings. Patients should not exceed the recommended dose on product labels, which must comply with these regulatory limits.

Resveratrol: Authorised high-purity trans-resveratrol products typically have maximum daily intake limits (often around 150-250mg daily, depending on the specific authorisation). While some research studies have used higher doses, these were investigational and are not recommended for self-administration. Patients should follow label directions and not exceed authorised limits.

When selecting supplements, patients should consider:

• Third-party testing: Look for products certified by independent testing organisations that verify ingredient purity and absence of contaminants

• Transparent labelling: Choose products that clearly state the amount of active ingredients per serving

• Reputable manufacturers: Select established companies with good manufacturing standards (e.g., HACCP, ISO 22000)

• Avoid exaggerated claims: Be sceptical of products making unrealistic promises about anti-ageing or disease prevention

• Check for additives: Some products contain unnecessary fillers, artificial colours, or allergens

Practical advice for patients: Start with lower doses to assess tolerance, take with food to minimise gastrointestinal effects, and maintain realistic expectations about potential benefits. Be aware that supplements containing piperine (black pepper extract) may increase the risk of drug interactions by affecting metabolism. These supplements should be viewed as part of a broader approach to health that includes a balanced diet, regular physical activity, adequate sleep, and stress management—factors with far stronger evidence for promoting healthy ageing.

When to contact your GP: Patients should seek medical advice if they experience persistent side effects, if they are considering supplements alongside prescribed medications, or if they have underlying health conditions such as liver disease, bleeding disorders, or metabolic conditions. Supplements should never replace evidence-based medical treatments, and any significant health concerns require proper medical assessment rather than self-treatment with unproven products.

Frequently Asked Questions