NAD+, NMN and resveratrol: can they slow ageing?

NAD+, NMN and resveratrol: what the claims mean

As interest in remaining younger for longer grows, the supplements market has expanded beyond creams and cosmetic solutions towards more ambitious products that say they can slow ageing by influencing cellular processes.

NAD+, NMN and resveratrol are among the most intensively promoted compounds. They are commonly said to support cell repair, energy production and healthy ageing.

Yet what do these substances really do, how are they being used, and how robust is the evidence?

To understand the claims, it is useful to distinguish between three separate things: NAD+ itself, the compounds marketed as ways of increasing it, and products containing these ingredients, including supplements, creams and serums.

Nicotinamide adenine dinucleotide, known as NAD+, is a coenzyme present in every living cell. Coenzymes are helper molecules that enable enzymes to perform chemical reactions in the body.

NAD+ is vital to energy metabolism, DNA repair, inflammation and the functioning of a group of proteins involved in cellular stress responses.

Levels of NAD+ generally fall with age, although the pattern is complicated and can differ across tissues. Reduced NAD+ availability has been associated with poorer mitochondrial function - that is, diminished activity in the cell structures responsible for helping to generate energy.

This is among the biological changes linked with ageing.

NAD+ in skincare and NAD+ precursors

NAD+ is now being included in skincare creams and serums, although the evidence in this area is even less developed than it is for supplements.

Although NAD+ matters for the energy and repair of skin cells, it is still uncertain whether NAD+ applied in standard creams can pass through the skin in adequate quantities to create meaningful anti-ageing effects.

Ingredients with a more established evidence base, including sunscreen, retinoids and niacinamide, currently have far stronger support for improving visible signs of skin ageing.

Since NAD+ itself is not believed to be absorbed effectively when taken orally, much of the research has concentrated on NAD+ precursors.

Precursors are substances the body can transform into another substance - in this instance, compounds it can convert into NAD+.

Two of the most familiar NAD+ precursors are nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR).

Animal research into NAD+ precursors has generated encouraging findings.

Older mice that received these compounds have demonstrated better energy metabolism, insulin sensitivity and certain aspects of physical function.

Some research has also found improvements in measures connected with healthspan and lifespan in animal models. However, results differ according to the model used and cannot be directly transferred to humans.

Such findings have fuelled huge commercial interest, but converting promising studies in mice into significant benefits for people has been considerably more difficult.

Clinical trials in humans indicate that NMN and NR can increase NAD+ concentrations, or related indicators of NAD+ activity, in blood and tissues. The most compelling evidence, however, relates to changes in the blood; evidence of meaningful effects within particular tissues remains limited.

A number of small studies have identified possible metabolic-health benefits, including improved insulin sensitivity in particular groups. Other studies have examined possible effects on muscle mass, but recent reviews have found no convincing evidence that NMN or NR maintain muscle mass or function in older adults.

The evidence becomes substantially less certain when studies assess outcomes that are more directly relevant to everyday ageing, including strength, cognition, frailty and biological age. Biological age is a disputed estimate of the body's apparent age at a cellular or molecular level.

One key challenge is that ageing takes place over a long timescale, whereas most supplement trials run for only weeks or months.

Resveratrol, benefits and limitations

Resveratrol is another compound frequently marketed for anti-ageing purposes, but it differs from NMN and NR. It is not an NAD+ precursor. Instead, it is part of a class of natural plant chemicals known as polyphenols, found in red grapes, berries and peanuts.

Laboratory and animal research has linked resveratrol with reduced inflammation and improved mitochondrial function - in other words, better activity in the parts of cells that help make energy.

The problem is that resveratrol has low oral bioavailability.

In practice, much of an ingested dose is broken down or altered before it can arrive in tissues at the form and concentration used in laboratory experiments. This leaves a major divide between what resveratrol can achieve in cells grown in a dish and what a supplement is likely to achieve in the human body.

To date, human trials have not provided convincing evidence that resveratrol slows ageing, while results concerning cardiovascular and anti-inflammatory benefits are still mixed.

Resveratrol can interact with certain medicines, particularly anticoagulant and antiplatelet drugs, which are often referred to as blood-thinning medicines.

Large doses may also lead to side effects, such as gastrointestinal symptoms. Anyone who takes regular medicines, has a chronic condition, is pregnant or is breastfeeding should obtain medical advice before using high-dose supplements.

So are NAD+, NMN and resveratrol the elixir of youth?

No. The crucial difference is between biological plausibility and demonstrated benefit. These compounds are not biologically implausible: they influence genuine pathways involved in energy production, stress responses and cellular maintenance.

However, changing a pathway does not amount to slowing ageing in a person.

In people, evidence to date points to possible benefits in restricted contexts, but important uncertainties persist over long-term safety, optimal doses and the people most likely to benefit.

The underlying science is plausible, but marketing often converts "this affects a process associated with aging" into "this supplement will keep you young".

For the moment, the best-supported ways of promoting healthy ageing are much less glamorous: exercising regularly, sleeping well, eating a balanced diet, not smoking, limiting alcohol and managing long-term health conditions.

Supplements could ultimately have a useful role, but the evidence for staying younger for longer is currently far stronger for everyday habits than for anti-ageing products.

Ahmed Elbediwy, Senior Lecturer in Cancer Biology & Clinical Biochemistry, Kingston University and Nadine Wehida, Senior Lecturer in Genetics and Molecular Biology, Kingston University

This article is republished from The Conversation under a Creative Commons licence. Read the original article.