The rise of NAD+
In recent years, different dietary regimens have emerged as a result of the exhaustive amount of research being done on our nutrient-sensing pathways and their relation to ageing. While much is known about the greatness of supplementing with specific amino acids, vitamins/minerals, or sports nutrition, another crucial molecule is yet to take the limelight.
Brace yourselves! It's time to acknowledge yet another molecule that your cells adore and could not live without.
The Precious Molecule You Ought to Know About
For the first time in June 2018, the World Health Organisation (WHO) added ageing to the 11th edition of its International Classification of Diseases, giving the nod to various committed scientists in pursuit of novel therapeutics to delay or reverse age-related diseases such as cardiovascular and metabolic diseases, cancer, obesity, and neurodegeneration.
A clear hallmark of ageing that has been observed across diverse species, including humans is a decrease in levels of the legendary molecule - Nicotinamide adenine dinucleotide (NAD+). The latter is in fact, a helper molecule and coenzyme present in literally all your cells. No worries, knowing the term NAD+ is enough. (scientists do the same!)
So what exactly is NAD+, and what makes us so keen for you to learn about it?
Functions of NAD+ & Why It Is So Important
Let’s dive to a microscopic scale.
From single-celled organisms like bacteria to yeasts, plants, and complex multicellular organisms like primates, NAD+ can easily be described as one of the most vital molecules across the kingdom of life. Besides being fundamental to energy metabolism, NAD+ is directly involved in a multitude of key processes such as in metabolic pathways and in cellular/DNA repair, thereby protecting your body from ageing and diseases. They help regulate your circadian rhythm (the natural internal process regulating your sleep/wake cycles) as well as maintain your neurotransmitter levels. Basically, all you ought to know about these superhero molecules is that they help to sustain life!
How is NAD+ Manufactured in Your Body?
A concinnity of interlocking biochemical reactions is responsible for your body’s production and regulation of NAD+.
The de novo pathway originates from the amino acid tryptophan - which can be found in food sources like meat, fish, eggs or fish.
The Preiss-Handler pathway where Nicotinic Acid (NA) - a form of vitamin B3 obtained from whole grains, meat and poultry - is the initial precursor of NAD+.
The salvage pathways where other NAD+ intermediates such as nicotinamide riboside (NR), Nicotinamide (Nam), or Nicotinamide Mononucleotide (NMN) lead to NAD+ synthesis.
In mammalians, NAD+ is predominantly produced and replenished through NMN, one of the reasons why NMN is also our favourite precursor. We will return to this molecule later on, but first things first - the biosynthesis of NAD+ comes with a catch…
NAD+ Production And Ageing
Unfortunately, your body does not have an endless supply of NAD+. In fact, clinical studies have shown how average NAD+ concentration seems to decrease by at least 50% over the course of adult ageing. Given the critical nature of NAD+ in the hundreds of biochemical reactions taking place simultaneously in your body, you might already take a guess on how this steady decline in tissue and cellular NAD+ levels may end up having major implications on your health.
Various scientists are describing this slow process of ageing as a cascade of vitality breakdown induced by a natural decline in NAD+ levels eventually leading to functional impairments in the body. NAD+ is like the fuel in your car; without it, you’ll end up crashing. As a matter of fact, alterations in NAD+ homeostasis have been linked to virtually all age-related diseases including cognitive impairment, cancer, metabolic diseases, sarcopenia, frailty, and obesity.
Solution To The NAD+ Crisis
Fortunately, it is possible to refuel your car!
According to Dr David Sinclair - biologist and genetics expert of Harvard University - and many others in the longevity field, ageing is a disease and a treatable medical condition. Indeed, the targeting of NAD+ metabolism is now looming as a potential therapeutic approach to extend longevity and delay the onset of diseases. Replenishing NAD+ levels in mice has repeatedly demonstrated promising results in delaying age-related diseases ranging from diabetes to Alzheimer’s, and more.
Note that animal models are primarily used due to their ridiculous anatomical, physiological, and genetic similarity to humans. For instance, rats, mice, and humans each have approximately 30,000 genes of which, about 95 % are shared by all the three species. Nonetheless, clinical studies on NAD+ are also in progress.
Why Does Boosting NAD+ Levels Work?
Over the past 30 years, scientists have amassed quality knowledge about a myriad of genetic pathways that underlie ageing phenotypes. Of these, sirtuins (SIRT1-7) - a family of NAD+ dependent enzymes - have been dubbed as longevity genes. Scientists even call them the ‘’guardians of the genome’’ as they play such a significant role in regulating homeostasis by sustaining genome integrity, promoting DNA repair, and maintaining a healthy circadian rhythm.
However, these proteins are ultimately useless without NAD+. In short, NAD+ is needed to activate those sirtuins which, in turn, will work hard to allow your cells to live healthier and longer, so you could do the same. Else, the entire system falls apart.
As the clock keeps ticking, your NAD+ levels keep decreasing. The good news is, science has once again got your back! You can now optimise your NAD+ levels and counteract the losses that come with ageing. Numerous studies show how supplementing with NAD+ precursors, including nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) can significantly increase NAD+ levels in your body again.
Wait, Why Precursors And Not Direct NAD+?
The administration of direct NAD+ supplements unfortunately does not work. This is partly due to their enormous size (cannot be absorbed by your cells) and their instability upon exposure to light, heat, or even water. Now, imagine the harsh conditions they'll encounter in your stomach - that’s no good at all! On the good side, you can still jack up the NAD+ level in your body by supplementing with NAD+ precursors like NR and NMN.
Our Personal Favourite - NMN
While NMN and NR both dance together in the realm of longevity supplements, recent studies highlight how NMN might actually be a better NAD+ booster than NR. Here’s why we also root for NMN when compared to NR:
As an intermediate, NMN is already one step ahead on its path to becoming NAD+.
NMN is significantly more stable.
NMN reveals more diverse and additional beneficial effects.
Esteemed experts are already consuming NMN supplements. For instance, Dr Sinclair takes it every day.
NASA is starting its research on NMN.
In fact, supplementation with NMN in animal models has been shown to increase NAD+ levels, suppress age-related inflammation, increase insulin secretion and action, enhance mitochondrial function, and ameliorate neuronal functioning.
Dr Shin-ichiro Imai made valuable progress in the ageing/longevity field with the impeccable discovery of crucial NAD+ dependent proteins like sirtuins and enzymes in mammals. He claims that NMN can improve adult human metabolism and make it resemble that of someone ten or twenty years younger. Currently a Professor of Developmental Biology and Medicine at Washington University School of Medicine, his aim is to ultimately achieve ‘’productive’’ ageing and develop effective healthy-ageing interventions.
At Avea, we are in the same boat! We firmly believe that boosting your NAD+ levels through NMN supplementation works, so we ask: Are you ready to live longer, happier and healthier?
Replenish your NAD+ levels!
Gain energy, restore vitality and embrace longevity with our NMN supplements. It is formulated with 250mg of NMN to help you maintain vibrant health for longer. A healthy lifestyle is about making healthy choices.