NAD benefits and side effects have become a topic of growing interest as research explores the role of nicotinamide adenine dinucleotide (NAD+) in cellular health and ageing. NAD+ is a vital coenzyme present in every cell, essential for energy production, DNA repair, and metabolic function. Whilst preclinical studies suggest potential benefits for cardiovascular health, neuroprotection, and cellular ageing, human evidence remains limited. NAD+ precursor supplements are generally well-tolerated, though side effects can occur. This article examines the current evidence for NAD+ supplementation, its safety profile, and important considerations for those contemplating its use within the UK healthcare context.

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. NAD 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.

Research suggests that NAD+ levels tend to decline with age in various tissues throughout the body. This decline has been associated with age-related physiological changes and metabolic dysfunction. Factors contributing to NAD+ depletion include increased consumption by DNA repair enzymes in response to cellular damage, reduced biosynthesis, and enhanced degradation by CD38, an enzyme whose activity increases with age.

NAD+ biosynthesis occurs through three main pathways: the de novo pathway from tryptophan, the Preiss-Handler pathway from nicotinic acid, and the salvage pathway from nicotinamide (the predominant route in mammals). Understanding these pathways has led to the development of various NAD+ precursor supplements, including nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and nicotinamide (NAM). It's important to note that in the UK, nicotinamide riboside chloride is an authorised novel food ingredient with specific conditions of use, while NMN is currently an unauthorised novel food and cannot be lawfully marketed as a supplement.

Evidence-Based Health Benefits of NAD Supplementation

Research into NAD+ supplementation has expanded considerably in recent years, though it is important to note that much of the evidence derives from preclinical studies, with human clinical trials still emerging. Cellular energy and metabolic function represent the most established areas of NAD+ influence. Studies suggest that NAD+ precursors may support mitochondrial function and cellular energy production, though clinical significance in humans remains under investigation.

In terms of cardiovascular health, preliminary research indicates that NAD+ supplementation might support vascular function. Small human trials have shown that nicotinamide riboside supplementation may improve arterial stiffness in middle-aged adults, though results have been inconsistent. Larger, longer-term studies are needed to confirm these findings and establish clinical significance.

Neuroprotection and cognitive function have garnered significant research interest. Animal studies suggest NAD+ precursors may support neuronal health, potentially through enhanced mitochondrial function and reduced oxidative stress. However, there is currently insufficient evidence from robust human trials to confirm cognitive benefits in healthy individuals or those with neurodegenerative conditions.

Regarding exercise performance and recovery, some evidence suggests NAD+ supplementation might influence muscle function. A limited number of human studies have reported effects on physical performance markers, though results remain inconsistent and require validation through larger randomised controlled trials.

DNA repair and cellular ageing represent areas of intense scientific investigation. NAD+ is essential for PARP and sirtuin function, both crucial for maintaining genomic stability. Whilst preclinical data are promising, there is no established link between NAD+ supplementation and extended human lifespan or prevention of age-related diseases. Claims regarding anti-ageing effects should be viewed cautiously, as human evidence remains preliminary.

It's important to note that in Great Britain, NAD+ precursors like nicotinamide riboside and NMN do not currently have any authorised health claims. Only niacin (vitamin B3) has certain authorised claims related to normal energy-yielding metabolism, nervous system function, and reduction of tiredness and fatigue.

Potential Side Effects and Safety Considerations of NAD

NAD+ precursor supplements are generally considered well-tolerated in healthy adults when taken at recommended doses, though comprehensive long-term safety data remain limited. The most commonly reported side effects are mild and gastrointestinal in nature, including:

• Nausea and stomach discomfort

• Diarrhoea or loose stools

• Flushing or skin warmth (particularly with nicotinic acid form)

• Fatigue or headache (reported occasionally)

• Indigestion or bloating

These effects typically occur at higher doses and often resolve with dose reduction or when taken with food. The UK Expert Group on Vitamins and Minerals suggests guidance levels of approximately 17 mg/day for supplemental nicotinic acid (to avoid flushing) and around 500 mg/day for nicotinamide.

Intravenous NAD+ therapy, which has gained popularity in some private clinics, may produce more pronounced side effects including nausea, cramping, and anxiety during infusion. This administration route carries additional risks such as phlebitis and infection. There is very limited published safety data for IV NAD+, it is not supported by robust clinical evidence, and is not provided by the NHS.

Important safety considerations include potential interactions with medications. Individuals with diabetes should be aware that high-dose niacin forms can worsen glycaemic control. Those taking statins should exercise caution, as niacin at lipid-lowering doses may increase the risk of myopathy. Individuals taking any regular medications should consult their GP before starting supplementation.

Contraindications and special populations require careful consideration. Pregnant and breastfeeding women should avoid NAD+ supplements due to insufficient safety data. Individuals with liver disease should exercise caution, as high-dose nicotinamide has been associated with hepatotoxicity in rare cases. Those with a history of gout should be aware that high-dose nicotinic acid can raise uric acid levels and potentially trigger gout attacks.

The regulatory status of NAD+ supplements in the UK means they are classified as food supplements rather than medicines, and are not subject to the same rigorous testing as pharmaceutical products. Quality, purity, and dosing accuracy may vary between manufacturers. Consumers should select products from reputable suppliers with third-party testing certification. If you experience any adverse effects, report them through the MHRA Yellow Card scheme.

Who Should Consider NAD Therapy and When to Seek Medical Advice

NAD+ supplementation may be considered by individuals seeking to support cellular health and metabolic function, though it is essential to maintain realistic expectations given the current evidence base. Those who might discuss NAD+ therapy with their healthcare provider include middle-aged and older adults experiencing age-related metabolic changes and those seeking to optimise cellular energy production as part of a comprehensive health strategy.

Athletes and physically active individuals sometimes consider NAD+ supplementation to support exercise performance and recovery, though evidence for performance enhancement remains limited. Similarly, individuals concerned about cognitive health may be interested in NAD+ precursors, but should be aware that human evidence for cognitive benefits is preliminary and does not currently support routine use for dementia prevention.

Before starting NAD+ supplementation, individuals should:

• Consult their GP or healthcare provider, particularly if they have existing medical conditions or take regular medications

• Discuss potential benefits and limitations based on current evidence

• Consider whether dietary and lifestyle modifications might address underlying concerns more effectively

• Verify product quality by selecting supplements with third-party testing certification

• Start with lower doses to assess tolerance before increasing

When to seek medical advice is crucial for patient safety. Individuals should stop taking the supplement and contact their GP if they experience:

• Persistent gastrointestinal symptoms that do not resolve with dose adjustment

• Unexplained fatigue, weakness, or muscle pain after starting supplementation

• Skin reactions, rashes, or significant flushing

• Changes in blood glucose levels (particularly relevant for diabetic patients)

• Liver-related symptoms such as jaundice, dark urine, or right upper quadrant pain

Neither NICE nor the NHS currently provide specific recommendations regarding NAD+ supplementation, as it is not considered a standard medical therapy. The NHS does not routinely provide NAD+ supplements or infusions, and individuals seeking such therapy typically access it through private healthcare providers. It is important to note that NAD+ therapy should not replace evidence-based medical treatments for diagnosed conditions, and individuals should not discontinue prescribed medications without consulting their healthcare provider. Lifestyle measures such as balanced nutrition, regular exercise, adequate sleep, and stress management remain the foundation of metabolic health.

Frequently Asked Questions