In recent years, NAD – nicotinamide adenine dinucleotide – has increasingly been called the molecule of youth, and supplements that raise its levels promise to help people stay healthy for longer and slow down ageing. But do these promises have a scientific basis? A study published in the prestigious journal Nature Metabolism, carried out by researchers at the Vilnius University Life Sciences Center (VU LSC) together with partners and involving more than 1,000 people, has revealed unexpected results: in the blood of healthy people, NAD levels do not decline with age, and in women they even increase.
The researchers also found an association between NAD levels and cardiovascular disease, especially hypertension. These findings encourage a fresh look at the role of NAD in the body and raise questions about the use of increasingly popular supplements.
The molecule of youth: how well founded are the hopes of halting ageing?
For millennia, humanity has been seeking ways to halt ageing and preserve youth for as long as possible. NAD is a molecule found in the living cells of the human body that is essential for energy production, metabolism, and many other vital processes.
This molecule has received considerable attention because research studies, conducted mostly on animal models and individual tissues, such as muscle, have shown that NAD concentration may fall with age. This popularised the assumption that restoring age-related losses of NAD might make it possible to slow down ageing processes. The hypothesis has prompted both a wave of new research and the growing popularity of dietary supplements that increase NAD levels.
According to Dr Dalius Ratautas, the VU LSC researcher who led the study, it was the wish to test these assumptions critically that led to the large-scale NAD research.
‘Our NAD study was intended to test one of the fundamental assumptions of NAD biology – whether the concentration of this molecule in human blood really does decline with age. We also wanted to find out whether NAD concentration is more closely related to a person’s state of health and chronic diseases than to ageing itself,’ said Dr Ratautas.
An unexpected discovery: NAD levels in women’s blood increase with age
To better understand changes in NAD in the human body, the researchers assessed how blood NAD levels relate to age, sex, and chronic diseases.
The results of the study did not confirm the assumption that blood NAD levels inevitably decline with age. NAD concentrations did not change significantly with age in healthy men and even increased in healthy women. The latter result was so unexpected that the researchers checked it more than once.
‘Personally, what surprised me most was the trend of NAD concentration increasing with age in the women’s group. I want to stress this point once again – according to our data, NAD levels in the blood of healthy women increase with age! We checked this result perhaps ten times – it was so unexpected. It illustrates how much we still do not know about NAD biology and why it is important to critically assess widely held beliefs,’ emphasised Dr Ratautas.
The study’s lead researcher explained that this discovery also highlights why it is important in medical research to ensure sufficient participation of women and to analyse data separately for men and women.
‘This is, by the way, an ideal example of why, in medical and metabolic research, it is important that women are adequately represented and that data is analysed separately by sex. Otherwise, one may fail to notice findings that apply to half of the population,’ the researcher pointed out.
NAD and heart disease: a new direction for medical research?
Another significant finding was the lower NAD concentration in the blood of people with cardiovascular disease. A particularly strong association was found between NAD levels and high blood pressure.
‘We found that in the blood of people with cardiovascular disease, especially hypertension, NAD levels are statistically significantly lower. Among people with other diseases, we did not find a statistically significant decrease in NAD levels, but confirming this would require further studies with a larger sample of people,’ said Kristina Ratautė, a medical doctor who was responsible for the clinical part of the study.
However, do lower NAD levels contribute to the development of disease or, conversely, do disease processes taking place in the body cause NAD levels to fall? For now, the researchers do not have an answer.
According to Ratautė, in the future it will be important to identify the specific biological mechanisms linking NAD metabolism to hypertension and other cardiovascular diseases. This knowledge could help in the search for new treatments, but further studies are needed first.
Is it worth taking supplements that increase NAD levels?
With growing interest in NAD and its links to ageing, supplements containing NAD precursors – nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) – are becoming increasingly popular on the market. The body can use these substances to produce NAD.
The researchers also analysed NAD concentrations in the blood of people who reported taking supplements that increase NAD levels. Some of them were found to have unusually high NAD concentrations. However, a higher NAD concentration does not necessarily mean better health or slower ageing. Moreover, the long-term consequences of unusually high NAD levels for the human body have not yet been adequately studied.
‘Our study did not assess the health effects of NAD supplements. Long-term, large-scale clinical studies that could reliably answer questions about the benefits and safety of these supplements are still needed. If NAD levels in the blood of a healthy person do not decline with age, the question arises – is there a need to increase them?’ reflected Ratautė.
So, although taking NAD precursors may raise the concentration of NAD in the blood, there is not yet sufficient evidence that such an increase helps people live longer or avoid age-related diseases.
Technology developed in Lithuania makes it possible to study thousands of people
An important part of this study is the technology the researchers developed for determining NAD concentrations. It uses dried blood spot samples taken by finger prick, making blood collection simpler and allowing studies to be scaled up easily.
‘The greatest advantage of the method is the ability to expand the scale of research easily. We are not limited to 1,000 volunteers – using this technology, we can study tens of thousands or even more,’ said Deimantė Stakelytė, who was responsible for the laboratory part of the study.
Particular attention was paid to the reliability of the method. The researchers compared the results from dried and liquid blood samples, conducted various control experiments, and involved several laboratories. ‘The reliability of the method is important because conclusions about human biology are drawn from the measurements. A large sample cannot correct systematic measurement errors,’ the researcher noted.
According to Stakelytė, the technology developed makes it possible not only to analyse NAD concentration in large groups of people but also to monitor how it changes over the course of a day, a week, or a month, and how it responds to physical exertion, diet, medication, or other factors.
The study is also an example of successful cooperation between research and business. It grew out of a collaboration between Vilnius University and the companies ‘SensoLife’ and ‘LifeLab1’.
The researchers hope that the technology developed through this cooperation and the results obtained will serve as the basis for further studies that will help researchers better understand the role of NAD in the human body and its links to health and ageing processes.