Nicotinamide adenine dinucleotide (NAD+) is a coenzyme essential for cellular energy production and metabolism in every living cell. As NAD+ levels naturally decline with age, interest has grown in supplementation strategies to maintain cellular function. For men, potential benefits span metabolic health, physical performance, and cognitive function, though the evidence base remains limited. This article examines what NAD+ is, how to increase levels safely, and the current evidence for men's health benefits. Understanding the regulatory status, safety considerations, and realistic expectations is crucial before considering supplementation.

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 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, in particular, regulate numerous cellular processes including DNA repair, gene expression, circadian rhythms, and mitochondrial function. These enzymes require NAD+ to function, consuming it in the process and converting it to nicotinamide.

Research suggests that NAD+ levels naturally decline with age, though this reduction varies by tissue type and individual factors. This decline appears to begin in adulthood and continues progressively, though the precise magnitude and timing differ between tissues. Several factors may contribute to this decline, including altered activity of NAD+-dependent enzymes, changes in synthesis from precursor molecules, and modifications in the salvage pathways that recycle nicotinamide back into NAD+.

The potential consequences of declining NAD+ levels may affect multiple physiological systems. Reduced NAD+ availability could influence mitochondrial function, DNA repair mechanisms, and metabolic regulation, primarily based on preclinical research. Understanding these mechanisms has led to growing interest in strategies to maintain or restore NAD+ levels, though the clinical significance of supplementation in humans remains an area of active investigation with limited conclusive evidence.

How to Increase NAD+ Levels Safely

Several approaches exist for potentially increasing NAD+ levels, each with different mechanisms and evidence bases. The most commonly studied method involves supplementation with NAD+ precursors—molecules that the body can convert into NAD+ through established biosynthetic pathways.

Nicotinamide riboside (NR) is an authorised novel food in Great Britain with a maximum permitted intake of 300 mg per day for adults (excluding pregnant and breastfeeding women). NR is converted to nicotinamide mononucleotide (NMN), which is then converted to NAD+ through the salvage pathway. Clinical trials have demonstrated that oral NR supplementation can increase NAD+ levels in blood cells, though tissue-specific effects vary.

Nicotinamide mononucleotide (NMN) follows a similar pathway, but importantly, it is not currently authorised as a novel food in the UK. Consumers should be cautious about purchasing unauthorised novel food products.

Nicotinamide (niacinamide) and nicotinic acid (niacin), both forms of vitamin B3, also serve as NAD+ precursors through different pathways. Nicotinic acid commonly causes flushing due to prostaglandin release, and high doses can cause hepatotoxicity and worsen glycaemic control. NICE guidelines do not recommend nicotinic acid for lipid modification. Nicotinamide typically does not produce these effects. The Reference Nutrient Intake (RNI) for niacin equivalents is 16.5 mg/day for adult men in the UK.

Lifestyle factors may also influence NAD+ metabolism, though human evidence is limited:

• Regular physical exercise has been associated with changes in NAD+ metabolism enzymes

• Caloric restriction or time-restricted eating may influence NAD+ pathways (though these approaches may not be suitable for people with diabetes, eating disorders, during pregnancy, or when taking certain medications)

• Adequate sleep supports overall metabolic health including pathways involving NAD+

• Dietary sources including meat, fish, nuts, and green vegetables provide niacin precursors

Before starting any supplementation regimen, individuals should consult their GP or a registered healthcare professional, particularly if they have existing medical conditions or take prescribed medications. Food supplements in the UK are regulated under food law by the Food Standards Agency (FSA) in England/Wales and Food Standards Scotland (FSS), while the Medicines and Healthcare products Regulatory Agency (MHRA) regulates medicines and medical devices.

Safety Considerations and Evidence Quality

The safety profile of NAD+ precursor supplementation requires careful consideration, as the evidence base remains limited compared to established pharmaceutical interventions. Nicotinamide riboside chloride has been assessed by the European Food Safety Authority (EFSA) and is an authorised novel food in Great Britain with a maximum daily intake of 300 mg for adults (excluding pregnant and breastfeeding women). Clinical trials have reported relatively few adverse effects at authorised doses. Commonly reported side effects include mild gastrointestinal symptoms such as nausea, bloating, or diarrhoea.

However, several important safety considerations warrant attention:

• Long-term safety data beyond 12 months of continuous use remain limited

• Drug interactions have not been comprehensively studied, particularly with medications metabolised through pathways involving NAD+-dependent enzymes

• Cancer considerations: some research suggests that whilst NAD+ may support healthy cellular function, cancer cells also require NAD+ for rapid proliferation; the implications for individuals with current or previous malignancies remain unclear

• Methylation effects: high-dose nicotinamide consumption requires methylation for clearance, though the clinical significance of this in typical supplementation is uncertain

The quality of evidence for NAD+ supplementation benefits varies considerably. Most human studies have been small, short-term, and conducted in specific populations. Whilst animal research has demonstrated promising effects on various age-related parameters, translation to human health outcomes remains uncertain. Many commercially available products lack independent verification of purity and content.

Individuals should be particularly cautious if they:

• Have liver disease (as NAD+ metabolism occurs primarily in the liver)

• Take medications for diabetes (potential effects on glucose metabolism)

• Have a history of gout (nicotinic acid can increase uric acid levels)

• Are pregnant or breastfeeding (insufficient safety data and excluded from novel food authorisation)

When to contact your GP: seek medical advice if you experience persistent side effects, unexplained fatigue, jaundice, significant changes in blood glucose levels, or any concerning symptoms after starting supplementation. Always inform healthcare providers about all supplements you are taking, as this information is essential for safe prescribing and monitoring. Suspected adverse reactions to supplements should be reported through the MHRA Yellow Card Scheme.

NAD+ Benefits for Men's Health and Wellbeing

Research into NAD+ supplementation has explored various aspects of men's health, though it is crucial to emphasise that much of the evidence comes from preclinical studies or small human trials with inconsistent results. There are currently no authorised health claims for NAD+ precursors like nicotinamide riboside or NMN in the UK or EU. The potential benefits should be viewed as preliminary findings requiring further investigation rather than established clinical facts.

Metabolic and cardiovascular health represents one area of interest. Some studies suggest NAD+ precursors may influence insulin sensitivity and glucose metabolism, parameters particularly relevant given the higher prevalence of type 2 diabetes in men over 40. However, human clinical trials have shown mixed results, with several studies finding no significant effects on insulin sensitivity or glucose metabolism. NAD+ supplements should never replace evidence-based approaches such as the NHS Diabetes Prevention Programme, or prescribed medications and lifestyle modifications recommended by healthcare professionals in line with NICE guidelines.

Regarding physical performance and muscle function, preliminary research has examined whether NAD+ supplementation might support exercise capacity or muscle health during ageing. The evidence from human studies is inconsistent, with several trials showing no significant effects on physical performance measures. The mechanisms might involve mitochondrial function in muscle tissue, though clinical significance remains uncertain.

Cognitive function has also been investigated, given that NAD+ metabolism changes in brain tissue with age. Animal studies have suggested potential neuroprotective effects, but human evidence is extremely limited. There is currently insufficient evidence to recommend NAD+ supplementation for cognitive enhancement or dementia prevention.

Some research has explored potential effects on testosterone levels and reproductive health, as NAD+-dependent enzymes are involved in steroid hormone synthesis. However, current evidence does not support claims that NAD+ supplementation significantly affects testosterone levels in men with normal endocrine function.

Fatigue and energy levels are frequently cited in marketing materials, based on NAD+'s role in cellular energy production. Whilst some individuals report subjective improvements, placebo-controlled trials have produced mixed results, and objective measures of energy metabolism have not consistently demonstrated significant changes.

Men considering NAD+ supplementation should maintain realistic expectations and prioritise evidence-based health strategies including regular physical activity, balanced nutrition, adequate sleep, stress management, and appropriate medical screening. The NHS provides comprehensive guidance on healthy ageing, including the NHS Health Check programme, and NICE guidelines offer evidence-based recommendations for managing specific conditions. Any supplementation should complement, not replace, these fundamental approaches to health maintenance.

Frequently Asked Questions