11m read|NOVOS

The Real Science Behind NMN Supplements

NMN (nicotinamide mononucleotide) is often touted as a supplement to slow down and even reverse aging. 

But what is the science behind these claims? Can NMN really slow down aging? 

And should we combine NMN with other anti-aging supplements

Let’s dive deeper into NMN, aging, and health. 

The science behind NMN

NMN is a substance that naturally occurs in our bodies. It can also be found in very small amounts in some foods, such as broccoli, avocado, and shrimp.

NMN is needed to build NAD+. 

NAD+ is a very important molecule. It’s found in all our cells. NAD+ can be considered as one of the main “fuels” enabling our cells to function properly. 

NMN (nicotinamide mononucleotide)

Without NAD+, there would be no life. NAD+ enables numerous proteins to carry out their tasks. 

Two important proteins that need NAD+ to function are sirtuins and PARPs. These proteins repair damaged DNA and help to maintain the epigenome.

Sirtuins are important molecules involved in aging. Sirtuins repair DNA and are needed for a healthy epigenome. When we get older, our DNA becomes more and more damaged, and our epigenome becomes increasingly dysregulated.

The epigenome is the complex machinery that surrounds the DNA and determines which genes are active and which ones are not. The older we become, the poorer the epigenome works, so some genes become active that should be switched off by the epigenome (like cancer-promoting genes), while other genes are switched off that should be switched on (like DNA repair genes).

PARPs are proteins that also repair damaged DNA. They are very dependent on adequate NAD+ levels. 

Unfortunately, when we get older, NAD+ levels decrease. This decline in NAD+ contributes to aging and plays a role in various aging-related symptoms and diseases, like metabolic, cardiovascular, and neurological problems.

By taking NMN, NAD+ levels can be increased, enabling NAD+ to drive proteins that repair, maintain, and protect our DNA, the epigenome, and many other parts of the cells.

Let’s explore some studies that examined NMN for lifespan, health, and longevity. 

NMN improves vascular health 

Aging of the blood vessels is a major contributor to the aging process in general. The biggest cause of death in most developed countries is due to diseased blood vessels (leading to stroke and heart attacks, for example). 

NMN can improve blood vessel health, especially in aged animals. Two important methods to assess the health of the blood vessels are the following:

– Endothelium-dependent dilation (EDD)

– Vascular stiffness

Endothelium-dependent dilation (EDD) is a measure of how healthy the endothelium is. The endothelium comprises the cells that line the blood vessels (these cells are called endothelial cells). The healthier the endothelium, the less atherosclerosis (clogging up of the blood vessels), and the better blood vessels can expand and relax. 

Vascular stiffness is another measure of vascular health. As a person gets older, blood vessels stiffen. This is due to crosslinking, accumulation of senescent cells, protein accumulation in the blood vessel walls, and other aging processes, which can all be accelerated by an unhealthy lifestyle. 

Multiple studies demonstrate that NMN improves vascular health. For example, in one study, NMN improved both endothelium-dependent dilation (EDD) and vascular stiffness to a significant degree, while also reducing oxidative stress in the blood vessel walls (R). 

Collagen and elastin were also higher in the NMN-treated mice versus controls, suggesting that NMN can increase collagen and elastin in the blood vessels, improving their elasticity.

Old mice that receive NMN (ONMN) have blood vessels that are as elastic as young control mice (YM) and young mice that receive NMN (YNMN). Old mice (OC) have stiffer blood vessels, reflected by higher pulse wave velocity or PWV (the stiffer the blood vessels, the faster the pulse wave travels through the blood vessels). 

Source: Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell, 2016

Old mice that receive NMN (ONMN) have blood vessels that dilate as well as young control mice (YC) and young mice that get NMN (YNMN). Dilatation of the blood vessels was considerably impaired in old mice that didn’t receive NMN (OC). 

Source: Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell, 2016

Elastin levels were substantially increased in old mice that received NMN (ONMN) compared to old control mice that didn’t receive NMN (OC). YC: young control mice. YNMN: young mice that received NMN.  

Source: Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell, 2016

The fact that NMN can have such strong positive effects on blood vessels is interesting in the view of aging. 

Aging of the cardiovascular system is an important driver of aging. The “vascular theory of aging” emphasizes the importance of the vascular system in our health and in the aging process.

For example, the cardiovascular system delivers food and nutrients to all our cells and removes waste products. Proper functioning of these processes is paramount for cellular health. 

Also, the surface area of the cardiovascular system is huge, and aged endothelial cells, called senescent endothelial cells, can secrete many harmful substances that are distributed throughout the body. 

So the adage “one is only as old as their arteries” could be very true. 

Another study showed that NMN, when given orally to mice, significantly improved the vascular system in elderly mice. NMN increased the number of capillaries (small blood vessels). Their endurance also significantly improved, indicating more blood flow to their muscles, enabling them to run on a treadmill for much longer.  

NMN supplementation significantly increases the density of capillaries (small blood vessels) in old mice receiving NMN (blue bars) vs. old mice not receiving NMN. 

 Source: Impairment of an Endothelial NAD +-H 2 S Signaling Network Is a Reversible Cause of Vascular Aging

Old mice that received NMN could run significantly longer on a treadmill compared to old mice not receiving NMN. 

Source: Impairment of an Endothelial NAD +-H 2 S Signaling Network Is a Reversible Cause of Vascular Aging

NMN boosts memory in elderly mice

The brain is very susceptible to aging. Various studies show that NMN can improve brain functioning in mice. 

For example, this study found that NMN significantly improved cognition in mice and blood flow in the brains of mice. The working memory of old mice receiving NMN was not only improved compared to old mice not receiving NMN, but the old NMN mice performed as well as young mice. 

Cerebral blood flow (CBF) is restored in elderly mice taking NMN (green bar) to similar levels as young mice (blue bar). The red bar represents old mice without NMN.
Source: Nicotinamide mononucleotide (NMN) supplementation rescues cerebromicrovascular endothelial function and neurovascular coupling responses and improves cognitive function in aged mice. Redox Biology, 2019

NMN boosts metabolism

When we get older, our metabolism declines. There are many reasons for this, such as mitochondrial dysfunction (the mitochondria are the power plants of our cells), epigenetic changes, increased insulin resistance, reduced nutrient signaling, and so on. 

Various studies demonstrate that NMN can improve blood lipids and insulin resistance and reduce aging-associated weight gain (R,R,R,R). 

Prediabetic women receiving NMN improved insulin sensitivity (R). Elderly men taking NMN (250 mg per day) improved muscle strength and performance (R). NMN also improved aerobic capacity in humans during exercise training (R). 

NMN reduces DNA damage

When we get older, our DNA gets more and more damaged. This is not a good thing, given that DNA contains the instructions to build and run our cells. 

Also, DNA damage needs to be repaired. But this repair process is not perfect, and DNA damage, even when repaired, can leave “epigenetic scratches,” which contributes to epigenetic dysfunction, an important cause of aging. 

NMN can reduce DNA damage in cells. In one study, old, untreated mice (O-PBS) had significantly more y-H2AX in their cells (y-H2AX is an indicator of severe DNA damage, like DNA strand breaks) compared to old mice treated with NMN (O-NMN): 

Liver cells in old untreated mice (O-PBS) had much more DNA damage compared to old mice treated with NMN (O-NMN). Y-PBS are young mice (alphaH2AX is a measurement for DNA damage).
Source: A conserved NAD+ binding pocket that regulates protein-protein interactions during aging, Science, 2017

In another study examining the DNA-protective effects of NMN mice got irradiated. Normally, such radiation leads to large amounts of DNA damage, destroying large amounts of red blood cells. However, when the mice were given NMN before radiation, they had significantly higher red blood cell levels compared to irradiated mice that didn’t receive NMN (as measured by hemoglobin levels).

NMN can protect mice when irradiated: hemoglobin levels (a protein present in red blood cells) was considerably higher compared to irradiated mice that didn’t receive NMN. 
Source: A conserved NAD+ binding pocket that regulates protein-protein interactions during aging, Science, 2017

NMN can improve fertility

The egg cells are one of the tissues in the body most susceptible to aging; some scientists believe that egg cells age much faster than many other tissues or organs. 

Egg cells age due to various reasons, including DNA damage. Studies in mice show that NMN can protect egg cells from DNA damage and can even partially restore fertility in old mice (R). 

We wrote a more extensive article about NMN and fertility here. 

Various biotech companies have experimented with NMN and NMN analogs to improve fertility in old animals, including old horses, with success. 


Interestingly, Harvard professor David Sinclair mentioned in his book Lifespan that an elderly family member who started to take NMN started to ovulate again despite having gone through menopause many years ago (R). 

NMN and general aging

Many studies demonstrated the powerful effects of NMN on slowing and even partially reversing various symptoms of aging in mice. 

For example, mice that were given NMN for 12 months orally (in their drinking water) improved multiple aging symptoms: NMN suppressed aging-associated weight gain, improved physical activity, enhanced energy metabolism, improved plasma lipids and insulin sensitivity, and ameliorated eye function (R,R,R). The authors of one study concluded that:

“These effects of NMN highlight the preventive and therapeutic potential of NAD+ intermediates as effective anti-aging interventions in humans.”

Professor Shin-ichiro Imai, Washington University School of Medicine, USA

Conclusion 

During aging, NAD+ levels decline in all our cells. NAD+ can be considered as the energy currency of our cells, or as one of the main cellular fuels. 

Providing NAD+ boosters like NMN have shown in countless animal studies to mitigate many symptoms of aging, such as improving metabolism, brain health, vascular health, eye health, stem cell function, and protecting cells against various stressors, including radiation and toxic molecules. 

In humans, we see that NMN can improve metabolism (R), muscle function (R), and energy levels (R). 

The science behind NMN has caused many people to take NMN for anti-aging purposes. One of its many scientific proponents is Harvard professor David Sinclair, arguably one of the world authorities on NAD+ metabolism, who takes NMN every day during his breakfast (learn more about David Sinclair’s longevity supplement routine here). 

There are various NAD+ boosters besides NMN, such as NR (nicotinamide riboside), niacin (vitamin B3) and nicotinamide (vitamin B3). However, we believe NMN is better than all these, and even better than NR, for various reasons we discuss in this article

If you take NMN, make sure the NMN is of high quality; lots of NMN bought online can be adulterated or have misleading claims of high purity. We explain more about how to pick the best NMN here. 

However, taking NMN is not enough to really make a dent in the aging process. We age not only because of declining NAD+ levels but also due to many other reasons, such as protein accumulation (due to a decline in autophagy, for example), epigenetic dysregulation, mitochondrial dysfunction (for example, due to copy errors in mitochondrial DNA), telomere shortening, crosslinking, and so on. 

Therefore, it’s important to always combine NMN with other science-based anti-aging supplements for maximal effect. We compiled a list with some of the best ones here


 

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