Hotwire Your Brain: How to increase NAD+ levels

Have you ever watched in horror as your printer runs out of ink right when you have an important document to print? Seeing each page come out worse than the last, blurry around the edges and fading? Well, imagine what it would be like for your cells. Running out of energy and power when you need them most.

That’s what happens with your mitochondria as we age. Mitochondria are our energy dynamos. They convert energy from food through cellular respiration and release it in the form of adenosine triphosphate (ATP), generating the chemical energy that our bodies use. That's why they're commonly called "cellular powerhouses".

As humans grow older, our mitochondria accumulate DNA damage due to oxidation and other environmental factors such as pollution, radiation, and inaccurate DNA replication. Imagine a photocopier taking increasingly grainy copies. According to current theories, this damage is the main cause of aging and neurodegeneration.

What repairs mitochondria?

The good news is that the majority of cells contain the ‘molecular machinery' to heal this damage. Repairs in the cell occur via the action of DNA repair enzymes - called sirtuins - which are fuelled by NAD (Nicotinamide Adenine Dinucleotide). Sirtuins contribute to longevity by maintaining the strands of DNA at the end of your chromosomes (telomeres), which are linked to life expectancy. What is NAD, you ask? Only the most prevalent molecule in the body, other than water! NAD is to humans what the AllSpark is to Optimus Prime. Without it, we’d die in seconds.

Nicotinamide Adenine Dinucleotide is essential to life and is found in all living cells. Everything that requires a metabolic reaction (even yeast and bacteria) relies on it. NAD serves as a source of energy for numerous vital biological processes, including:

Converting nutrients into ATP (the universal cellular energy currency)
Strengthening cells' resistance to oxidative damage
Setting your body’s metabolism and circadian rhythm (internal clock)

And perhaps most importantly:

Activating DNA repair enzymes to restore damaged mitochondria.

Age-related decline in NAD levels: the bad news.

However, here's the kicker: enzyme activity burns through up NAD molecules during your lifetime, making it increasingly harder to defend against the detrimental effects of oxidative damage and the genotoxic factors that destroy DNA. It's a vicious circle. It's a fuse running out on the timebomb of cellular death. At the University of New South Wales, researchers sampled the NAD content in human skin tissue at various ages. Despite being found in every cell throughout your body, the availability of NAD declines dramatically. By the age of 20, you have about half the store you were born with, and that almost halves again at age 40, and so on every 20 years until death.

We not only produce less NAD as we age, but we also require more of it to keep our cells in balance. To return to our "molecular photocopy machine" analogy, the blurry mitochondrial DNA codes are transcribed from a copy of a copy - all the while as the machine runs out of toner! The symptoms of mitochondrial damage may manifest as:

Increased rate of cognitive decline
Chronic fatigue and decreased energy
Lowered metabolism
Accelerated internal ageing
Increased inflammation in the body

So the question becomes, how do we combat low NAD levels? Importantly, NAD itself can't be easily ingested from food sources, as it is notoriously hard to absorb. The enzymes in the lining of your digestive tract need to break down NAD several times in order for it to be absorbed - by which time the delicate molecule is all but destroyed. Unfortunately, ingestible NAD is not an effective option. Some people go to the extreme of intramuscular or intravenous injection to top up their NAD levels. While there are enthusiastic fans of this type of "brain reboot", it is not without risk.

So how do we get the body to produce more NAD? We are born with a full supply of NAD that we use up across our lifetime. But it is constantly recycled, and we can biohack that process to ensure it runs more effectively by feeding mitochondria.

Increasing NAD with NMN supplements: the good news.

Recent research suggests it may be possible to reverse mitochondrial decay with dietary supplements that increase cellular levels of NAD through its precursor NMN (Nicotinamide Mono Nucleotide). NAD is the key that drives the mitochondria to produce energy, but NMN is the spark that can power up your tired mitochondria.

Here's where we have to dive into the science. NAD actually gearshifts between its two forms, NAD+ and NADH (nicotinamide adenine dinucleotide and hydrogen), by accepting electrons then allocating them to other processes like metabolism, DNA repair, and cell communication. NAD+ is the "high energy" molecule that facilitates cellular processes, whereas NADH will give up its electrons to other molecules and be converted back to a closed-shell form of NAD+. NMN supplies extra electrons in this loop, which is known as the NAD Salvage Pathway, replenishing the stock of NAD+ and preventing the cells from going into a state of low-energy hibernation.

We can boost NAD+ by activating the enzyme NMN adenylyltransferase, which helps convert NADH (the 'empty' return molecules) back into NAD+. The rate at which this happens improves healthy mitochondrial function - which is important because of the relatively short half-life of our age-limited lifetime supply of NAD. You want to ensure it's recharging the degraded NAD as efficiently as possible.

It's all part of a vast molecular fuel supply chain - providing the NAD with NMN, so that it can fuel the sirtuins that rejuvenate the mitochondria, which in turn release adenosine triphosphate. For a sense of scale and how pivotal this process is, cells in the body use approximately one billion ATP molecules every minute. It all starts with the right nutritional components to activate the genes and enzymes that then do the work for us - the same superstar micronutrients found in Simply Nootropics Elevate.

What health benefits might you experience?

It's worth noting that research on Nicotinamide Mononucleotide (NMN) is still in its early stages. It's a relatively new field; researchers have only really studied the age-reversing capabilities of NAD and NMN's key role in boosting NAD levels since 2013. Both these studies were spearheaded by Dr. David Sinclair, professor of genetics at Harvard Medical School. In fact, Dr. Sinclair has dedicated his career to researching NMN, and his breakthrough non-fiction book Lifespan: Why We Age - and Why We Don't Have To (2019) is essential reading for every biohacker.

Dr. Sinclair hacks with NMN himself, but he is upfront that it's a personal choice, and he doesn't advocate that others necessarily should or shouldn't copy him; it's up to everyone to make their own informed decision. Partly this hesitancy is due to the lack of human trials because NMN is so cutting-edge. Dr. Shin-ichiro Imai, another researcher at the forefront, notes "There are already thousands of people who are taking NMN, I have heard some anecdotal stories. So far, what I have heard is interesting... We need to prove the efficacy scientifically in human clinical trials.”

It's actually only in 2021 that the first studies in humans were published, and these were baseline studies to establish safety and tolerance (and they concluded that up to 500mg of NMN is safe in healthy men). However, animal studies and first-hand testimonials from early adopters tout positive results and indicate that NMN may:

A word of caution: potential risks

Like Dr. Sinclair and Dr. Imai, we think biohackers should make up their own minds. That's why we encourage you to do your own research and weigh up the potential benefits and risks. It's important to note that there are some theories that boosting NAD+ may exacerbate existing tumours because stimulating cellular activity applies indiscriminately, to good and bad cells alike. In fact, intentional inhibition of the NAD Salvage Pathway is being explored as a possible therapeutic treatment. As always - especially if there is a preexisting condition or health concern - consult with your doctor. This blog is for educational purposes only and is no substitute for a medical professional's advice. It is currently believed that NMN is safe and metabolized in healthy men without any substantial side effects. However, the trial was brief and only included a small number of people (N=10). More thorough testing is required. Clinical trials to establish safety with greater confidence are currently taking place.

Smart move: The brain benefits of NMN

For now, NMN has already shown promising signs of reversing mitochondrial decay. In addition to promoting the age-reversing abilities of NAD, NMN shows potential in boosting mental performance and protecting against age-related cognitive decline. NMN has been observed to have powerful brain effects on mice (which translate to humans). Dr. Shin-ichiro Imai and colleagues at Washington University in St. Louis have found that administering NMN to mice can restore their mitochondrial function to levels similar to those seen in younger mice, as well as improving certain aspects of brain function. In particular, studies have shown that NMN supports improved cognitive function by rejuvenating brain cells so they can regain normal function.

This means NMN may improve your mental performance and focus, help create long-term memories, and ultimately protect against their loss. We all want to live longer - and NMN can assist us in keeping our brains performing at their best as we age! Three specific areas that show significant improvement in mice studies include:

Alleviating Age-Induced Cognitive Impairment. NMN slows cognitive decline by increasing energy, regenerating cells, and slowing down the aging process. NAD+ supplementation acts on neurons to support synaptic connections, and supports mitochondrial function, which is key to maintaining a healthy brain.
Preventing Vascular Cognitive Impairment. Lower NAD+ levels are responsible for many cardiovascular related neurodegenerative diseases. NMN may have a positive impact on your blood pressure, as it enhances vasodilation. Boosting NMN improves circulation, stopping brain cells dying from poor blood flow.
Combating Alzheimer’s and Parkinson’s disease. Related to the two above: researchers believe both oxidative stress and impaired mitochondrial function are behind age-related brain disorders such as Alzheimer’s and Parkinson’s. The protection that NHN provides against oxidative damage - and its potential to reduce mitochondrial fragmentation - is a powerful two-punch combo. NMN may be able to inhibit these diseases and preserve the brain against them.

It's still not fully understood how helpful it is to raise NAD+ levels in people with age-related brain disorders. More human trials are needed. However, preliminary studies suggest positive outcomes. NMN may improve memory, cognitive function, and age-related cognitive decline. It also shows promise for improving mental performance and preventing neurodegeneration by protecting the brain from daily stressors and disease, and keeping it powered with the energy you need to stay active and alert.

Conclusion

Feel like you're always tired and exhausted? Constantly reaching for the double-edged sword of coffee or caffeine to keep you going throughout the day? Then NMN may be what your body is crying out for. Although NMN is found in healthy food such as broccoli, avocado, and cucumber, taking NMN as part of a nootropic stack boosts NAD levels well above what any dietary measure alone can provide.

This makes it the preferred source of the cellular rocketfuel that is in short supply as we age (or when mitochondria are struggling due to poor diet, high-stress levels, or lack of sleep). NMN might be the kick you need to power-up your mitochondria, so they are no longer struggling to keep up with daily demands. Feed the dynamo with Simply Nootropics Elevate!