NAD+ Supplement Therapy Benefits

NAD+ Supplement Therapy Benefits

Article Highlights

  • NAD+ is an essential molecule for energy (ATP) production in all cells.
  • Sirtuins are protein enzymes that use NAD+ and “turn off” aging, inflammation, fat synthesis and storage and insulin resistance related genes.
  • With the help of NAD+, sirtuins help to guard the genome and serve many important functions that we continue to learn more about in terms of anti-aging.
  • NAD+ is made from niacin, vitamin B3, that exists in the oxidized and reduced form and helps with the conversion of food into energy.
  • NAD+ is important for mitochondrial health and declines as we get older.
  • Low NAD+ levels adversely affect mitochondria and contribute to aging and disease.
  • NAD+ shows promise as a treatment for neurodegenerative and metabolic conditions.
  • NAD+ is used in the treatment of drug and alcohol addiction.
  • When it comes to NAD+ supplementation, liposomal NAD+ offers superior absorbability and bioavailability compared to NMN and NR “precursors” which need processing by the body to become NAD+.

What if I told you there were a special nutrient that your body makes from a simple B vitamin, which helps to keep you young and energetic?

Well, it’s true and this nutrient is NAD+.

I’m always amazed in medicine when it’s the simplest of interventions that deliver profound and wide-reaching results. NAD+ might just be a key piece to anti-aging medicine, chronic disease prevention and even recovery from addiction.

The first time I ever tried NAD+ was as NAD IV therapy.

By the time the intravenous NAD+ infusion was over, I was already experiencing subtle changes: my vision was sharper, I felt calmer, I had the energy for a great workout and overall I felt a heightened sense of wellbeing. I continued to see benefits after subsequent infusions.

But not everyone can get an intravenous infusion. And honestly NAD+  is time consuming to infuse cases. In many cases it will cause an unpleasant, benign sensation of muscle tightening when the infusion drip is too fast. At slow drip rates this sensation immediately goes away, it’s a benign effect but it places time constraint limits on the IV infusions which can sometimes take 3-4 hours.

Since IV NAD+ is not available to everyone and can be quite expensive, I began looking into how to bring this vital nutrient to more people in a way that was effective like an IV, but also more affordable and accessible to those who could benefit the most.

And since we all age and are more susceptible to disease as we get older, there are a lot of people who can benefit from this simple and effective therapy.

The main issue with making an oral supplement had always been that NAD+ is a finicky and unstable molecule. This is why most NAD supplements on the market are “precursors” like NMN or NR, molecules that the body may use to manufacture its own NAD+.

But you will see later in the article that NAD+ itself IS now available and in addition we have come up with a high absorption oral “liposomal” form that you can try for yourself without having to sit through an IV session. (If it’s already something you know you want to try, check it out by clicking here).

In this article, you’ll learn more about:

  • What is NAD and niacin NAD+ precursor
  • The role of NAD+ in energy metabolism
  • NAD+ and sirtuins in aging and disease
  • NAD+ supplement use in disease
  • NAD+ in the treatment of addiction
  • Liposomal NAD+ supplements

Niacin, an NAD+ Precursor

Let’s start with the basics. What is NAD?

NAD+ is derived from niacin, which is vitamin B3. Vitamin B3 is an essential nutrient that we need to get from our diet on a regular basis. NAD is found in all living cells and is essential for life. Without it our cells cease to exist.

NAD stands for Nicotinamide Adenosine Dinucleotide, which acts as a coenzyme in every cell, and specifically 70% of it is concentrated in the mitochondria of cells where energy is made (Source 1). A coenzyme is like a helper: it’s needed for the chemical reaction to occur and helps the enzyme to complete the reaction.

NAD+ helps us to produce energy in the form of ATP.

NAD switches between two molecular forms, NAD+ and NADH, and it is involved in something called “redox,” or reduction-oxidation, reactions.

NAD+ is the oxidized form, which is considered the “active” form: it actively accepts two electrons along with a hydrogen from another molecule to form NADH. It’s this electron exchange that produces energy.

NADH is the reduced, or inactive form of NAD. In order for the cell to continue producing energy, NADH needs to be recycled back into NAD+. If that recycling stops, NADH accumulates and the cell runs out of energy. Cells need a continuous supply of energy in order to function, so without NAD+ cells die. (Source 2)

In the diagrams below, you can see the how the full molecule of NAD+ is synthesized. The structures and function become important when we talk about supplementation.

Unfortunately, as we get older NAD+ levels naturally decrease and mitochondria become less efficient.

Drugs, alcohol, medications, stress, toxins, inflammation, chronic disease and other factors accelerate this decline. As NAD+ goes down, so does our energy. Cells age more quickly causing a loss of vitality and contributing to disease.

You might be tempted to stop reading and immediately start a search for “NAD supplement” to buy online since NAD+ is so crucial. However you will notice that it is very hard to find actual NAD+.

Most of the supplements out there sell a “precursor” molecule and not NAD+ itself.

In other words they supply a different type of molecule, like NMN (nicotinamide mono nucleotide) or NR (nicotinamide riboside) which are not as impactful because our cells need to spend energy to convert these precursors to manufacture into NAD+.

But the ultimate goal is to provide cells with the finished product: NAD+. Read on to see what we have achieved with our Liposomal NAD+.

NAD+ And Energy Metabolism

Now that you understand how NAD+ is used up and then recycled and how essential it is, let’s talk about the specifics of NAD energy metabolism. I walked through this mitochondrial process in greater detail in a previous article, but here is a little recap from the perspective of NAD+.

Let’s take a molecule of sugar (glucose) that is absorbed into your body from food. The sugar moves from the bloodstream into a cell where it is split into 2 molecules called pyruvate. This is called glycolysis and it requires two molecules of NAD+ to produce two energy molecules of ATP and 2 molecules of NADH that needs to be recycled.

Then, pyruvate turns into acetyl CoA, which also requires 2 molecules of NAD+. Next, the acetyl CoA enters the mitochondria into the Citric Acid Cycle, requiring 3 molecules of NAD+ for each turn of the cycle. Then, NAD+ becomes the star of the show, for the final step of ATP (energy) production in the cell. Electrons pass across the inner membrane of the mitochondria to produce energy.

If all this feels a little too much like high school biology, the bottom line is that NAD+ is an essential intermediate in the mitochondrial processes that turns not just sugar, but proteins and fats, into energy. 

Bottom line: We can’t get energy from the food we eat without NAD+.

When NAD+ becomes depleted, it contributes to mitochondrial dysfunction, which I discuss in my recent article on acetyl l carnitine and alpha lipoic acid. When the mitochondria aren’t happy and functioning well, we increase our risk for developing a host of chronic conditions from autoimmune disease to metabolic disease like diabetes.

NAD+ And Sirtuins In Aging And Disease

If we look at NAD levels by age, it’s clear that NAD+ in tissues decrease over time. It’s often noted that levels decline around 50% by the time we are 60 years old. (Source 3)

The age related NAD+ levels can be directly attributed to the enzyme NAD+ Nucleosidase, or “NADase CD38” for short.

CD38 enzymes use up NAD+ (and it’s precursor NMN) depleting NAD+ stores inside cells and causing an energy shortage.

CD38 is also linked to chronic inflammation, which is a root cause to chronic disease. In addition, CD38 is linked with declining mitochondrial function (Source 4), which becomes important as we talk about the role of NAD+ in fatigue and chronic fatigue. It’s no wonder that disease rates also increase with age! (Source 5)

While NAD+ levels decrease with age, NADH (inactive) levels increase. The NAD+/NADH ratio decreases as we age as NAD+ converts to NADH and cannot be converted back to NAD+.

In fact levels of NAD+/NADH levels are directly correlated with aging muscles and increased oxidative stress placed on catabolic organs. (Source 3)

With cellular aging, it also becomes harder for the body to synthesize NAD from niacin. This loss of NAD is associated with aging as well as age-related metabolic disorders and neurodegenerative disease. (Source 6)

So, if depletion of NAD+ leads to aging and disease, does restoring NAD+ have the opposite effect?

Is NAD treatment the fountain of youth?

To understand the role of NAD+ in longevity and anti-aging, we have to take a look at the sirtuins connection. Sirtuins are the reason why NAD anti aging research is such a hot topic.

Sirtuins, or SIRTs actual name is “NAD-dependent histone deacetylase enzymes” and they exert epigenetic regulation of gene expression. In other words they can turn genes “on” or “off”. Often the genes they turn “off” are involved in aging.

But SIRTs are a big family of enzymes that play other roles like  regulating cellular health and homeostasis, energy metabolism and mitochondrial function. Additionally they are  important for the cell “stress response”,  coordinating repair when a cell is damaged.

The sirtuins and NAD connection is this: sirtuins need NAD+ to achieve their functions. (Source 7, 8)

There are seven SIRTs and we are understanding more about them all of the time. Here’s a quick breakdown.

  • SIRT1 – associated with longevity, plays a role in amyloids in the brain, which have been linked to neurodegenerative disease
  • SIRT2 – associated with longevity through gene regulation
  • SIRT3 – associated with longevity, reacts to nutritional status, helps the body adapt to calorie restriction
  • SIRT 4 and SIRT 5 – are found in the mitochondria and we are still learning about their importance
  • SIRT 6 – important for DNA repair and defending against oxidative stress, plays a role in the NF-kB pathway and may reduce inflammation
  • SIRT 7 – has been identified, but not much is known yet (Source 7)

To simplify, the SIRT proteins appear to “turn off” genes that promote aging, including those that cause inflammation, fat synthesis and storage and blood sugar management issues. Because of these roles, SIRTs are known as “guardians of the genome.”

Up until now the only way we knew to positively impact these SIRT enzymes was to go on a very low-calorie diet. As uncomfortable as it may be, caloric restriction is one of the few ways that has repeatedly been shown to lead to a longer life.

However, the tide appears to be turning. You see, recent research indicates that NAD+ plays a key role in the creation and activation of the sirutins.

Doctors out of the Department of Developmental Biology at the Washington University School of Medicine were the first to show this link in 2014. The authors note:

“NAD(+) levels decline during the aging process and may be an Achilles’ heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD(+) by supplementing NAD(+) intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases.” (Source 6)

These findings were corroborated in 2016 when the scientific journal Rejuvenation published an article where the authors discussed how low NAD+ levels are directly associated with cellular aging, and they emphasized that this process can be prevented by increasing the levels of NAD+ within cells. (Source 9)

NAD+ assists in DNA repair:

Another role for NAD+ is to catalyze a set of enzymes called poly adenosine diphosphate ribose polymerases which we will call PARPs for short. These enzymes go around repairing DNA (“broken” DNA can have a direct role in initiation of cancer) but they will not work without the availability of NAD+. (Source 3)

I also want to point out that NAD supplementation is linked with lengthening telomere’s, the “tails” on DNA that determine our biological age. (Source 10) This likely plays a role along with what I’ve discussed here.

So is NAD+ a fountain of youth? It could be. More research needs to be done, but current evidence is beginning to paint the picture that NAD therapy, through oral supplementation or NAD IV, may increase both the lifespan and health span. (Source 9, 11)

One thing seems clear: nicotinamide benefits the body at the cellular level, and it may just turn back the hands of time.

NAD+ And Chronic Disease

The link between NAD+, energy production, and chronic illness really couldn’t be clearer. Low NAD+ results in low ATP levels.

Low ATP levels quickly depletes your cell’s energy reserves. When a cell’s energy supply isn’t replenished, the cell ages and can die.

Depending on the types of cells that are affected by the low NAD+ levels, different diseases might develop over time. If nerve cells are affected, depression, anxiety, fatigue or a lack of focus may show up as the symptoms of this cellular lack of energy. In other cases, one might experience tremors, spasms, tingling, numbness and blurred vision. Symptoms can be transient or, in more extreme cases, lead neurodegenerative conditions such as Parkinson’s disease or Multiple Sclerosis.

All of the knowledge of the role NAD+ plays in energy metabolism and anti-aging has led to therapeutic applications of NAD supplements in a variety of cases. A 2015 review article recommends NAD+ supplementation as a therapy for a wide range of neurodegenerative disease including:

  • Multiple Sclerosis
  • Parkinson’s disease
  • Alzheimer’s disease
  • Chronic fatigue
  • Fibromyalgia
  • Mitochondrial dysfunction (Source 11)

Because of the importance NAD+ for both energy metabolism and sirtuins, research is looking at its use for metabolic disease. There is growing evidence in animal models of this connection, but human trials are still scarce. (Source 12) It will be interesting to follow the science as the use of NAD+ evolves for diabetes, obesity, heart disease and other metabolic conditions.

I’ll talk more about how to supplement with NAD at the end of the article, as far as the form and dosages, but first, let’s take a look at some of the ways NAD is being used clinically, with the most compelling human research for chronic fatigue syndrome, Parkinson’s disease and athletic performance.

Chronic Fatigue Syndrome (CFS):

A few strong clinical trials show that NAD+ may reduce symptoms of CFS including fatigue, muscle pain, weakness, headaches and others. In an early (1999) randomized crossover trial, 31 percent responded favorably to the supplement, compared to only 8 percent of placebo in just 4 weeks of use. (Source 13)

Since that time, larger trials have shown similar results. In a study of NAD+ and Coenzyme Q10, an important mitochondrial antioxidant, showed that those receiving the supplements had a significant reduction in fatigue, along with improved levels of NAD+, CoQ10, ATP and Citric Acid Cycle enzymes. (Source 14) In an 8 week study of NAD+ and CoQ10, symptoms of fatigue also improved using an exercise test. (Source 15)

Parkinson’s Disease:

The use of NAD+ supplements may increase dopamine production in the body, leading to various clinical applications from Parkinson’s disease to improvements in mental health. (Source 16) The enzyme, tyrosine hydroxylase, is diminished in the brains of people with Parkinson’s Disease and NAD+ has been shown in animal models to increase this enzyme activity along with dopamine levels. (Source 17) In a small, 7-day trial, Parkinson’s patients showed a significant response to supplementation in terms of both dopamine production and decrease in symptoms. (Source 18)

Cardiovascular Health:

In a study of healthy individuals between the ages of 55 and 79, participants received either nicotinamide riboside (a precursor to NAD+) or placebo. The study found that those in the treatment group tolerated the supplements well and they showed a 60 percent increase in NAD+ levels, with a potentially greater response in those with lower levels to begin with. In addition, the study looked at a variety of metabolic markers and although authors suggest more research is needed, there is evidence that the supplementation may help to improve blood pressure and the health of the arteries. (Source 19)

NAD+ And Wellness

While much of the research resides in the use of NAD+ for chronic, degenerative conditions, NAD+ may also be beneficial for both exercise performance and sleep, and along with its anti-aging benefits, contributes to overall wellness.

Athletic Performance:

With exercise, ATP (energy) is used by muscles, this depletes NAD+ and raises NADH levels. A 2010 study showed that using pycnogenol, a pine bark extract, supports the recycling of NADH back to NAD+ and raises NAD+ levels. Supplementation was given to both trained and untrained athletes in a small trial and it showed increased exercise performance and also  increased  “time to fatigue.” (Source 20

Better Sleep:

Improved sleep is a well-known benefit of NAD+ in the IV world and I’ve personally had similar results when taking Core Med Science’s Liposomal NAD+. This may be due to the role that both NAD+ and SIRT1 play in maintaining a balanced circadian rhythm. (Source 21) In addition, SIRT1 is found in “wake neurons” in the brain and as this sirtuin declines with age, it may impair wakefulness. (Source 22)

NAD+ Treatment For Addiction

Another interesting area of research on supplemental NAD+ is in the treatment of addiction. NAD+ plays a role in reducing cravings to addictive substances, including alcohol and drugs, and helps you to safely withdraw from these chemicals.

There are many clinics around the US now that use NAD+ IV infusions to assist in the treatment of chemical dependence and detoxification. NAD+ allows for a much gentler withdrawal from drugs (benzodiazepines, opioids, etc.) and alcohol. The two centers I recommend are Dr. Ken Starr’s clinic in Arroyo Grande, California and The Springfield Wellness Center in Springfield, LA.

Here is how NAD+ works in the case of alcohol detoxification as an example. When alcohol (ethanol), is in your body, the liver works hard to eliminate each and every molecule of alcohol. Alcohol is converted to acetaldehyde with the enzyme alcohol dehydrogenase and NAD+ is critical to this process. Alcohol donates one hydrogen molecule irreversibly to NAD+ converting it to NADH. Alcohol thus depletes NAD+.

That NAD+ molecule is now gone and the NADH in your system begins to build. As this happens repeatedly, the NAD+/NADH balance swings out of favor, and you run out of NAD+. You will feel the symptoms of a hangover and an uncomfortable withdrawal because your body can’t effectively detoxify. 

In a 2012 review article, the authors conclude that it is this NAD+ depletion and NADH accumulation that disables the mitochondria in your liver cells from being able to make energy ATP. This leads to liver cell death. Your body is then even less capable of processing the alcohol out of your system, which may set the stage for chemical dependency. (Source 23)

NAD+ and SIRT1 play a role in the rhythm of dopamine production, which contribute to the physiological “reward” system for cocaine. (Source 24) One reason that NAD+ may support addiction recovery is because of the improvement of dopamine levels, through the mechanisms discussed with Parkinson’s disease.

As I mentioned above, both supplemental NAD and NAD IV therapy are used in addiction treatment centers with promising results. Clinical benefits have been reported from opioid withdrawal. (Source 25) There is much more to be learned in this area as well, but since the safety of NAD treatment for addiction is high and we have more understanding of how NAD+ plays a role in metabolism and sirtuins, I’d expect that we will see some clinical trials in the years to come.

Liposomal NAD+

Is an NAD supplement right for you?

A common question: does niacin increase NAD+ levels? While our bodies make NAD+ out of niacin (vitamin B3) and other precursors, production might not be able to keep up with our cellular demands for NAD+ with aging and disease. I still recommend getting good whole food sources of niacin in the diet from foods like liver, chicken, turkey, salmon, beef, liver, brown rice, mushrooms and cooked tomatoes. Foods rich in tryptophan also contribute to NAD+ production and these include many of the same animal proteins.   

In addition to including food sources to contribute to NAD+ production in the body, exercise, fasting and supplementation are other lifestyle tools often used to support healthy levels.                                                                             

When it comes to niacin supplements, the main downside is that higher dosages cause flushing. Taking nicotinamide supplements has been shown to avoid this uncomfortable side effect. The most common supplemental forms are nicotinamide ribose and nicotinamide mononucleotide, however these common forms aren’t as effective as NAD+ itself.

You’ll see many NAD supplements on the market in the form of NMN (nicotinamide mononucleotide) or NR (nicotinamide ribose) precursors, which need to be processed by our cells to make NAD+ which requires the use of ATP. If you are already running low on energy, this conversion process might not work very well. And, you might actually feel worse with these supplements. 

Here is a diagram of this conversion process:

As you can see, if you supplement with NAD+ instead of one of the precursors, NR or NMN, you save this additional step (or steps) and can get the benefits of NAD+ directly, and right away.

The studies often used to promote NR supplementation, were done on animals, and not humans. Evidence suggests that oral NR or NMN supplements aren’t absorbed and don’t make it much farther than the liver. Additionally, these precursors may interfere with methylation. (Source 26)

As you can see, there are potential downsides to the popular NAD supplements that are actually NAD+ precursors. So what about supplementing NAD+ itself?

Enter Liposomal NAD+!

A liposome is a phospholipid container that carries the NAD+ into the body and into the mitochondria of the cells. Since liposomes have the same structure as cell and mitochondrial membranes this is a very effective and efficient delivery system.

It might take 1000-2000mg of NR (nicotinamide riboside) to increase levels of NAD+ in the body (Source 12), however, with a liposomal product, a much lower dose is effective. Core Med Science’s liposomal product contains 100mg of active, stable, highly absorbable NAD+ in a phospholipid derived from sunflower, so it’s allergen and GMO-free.

While it may sound too good to be true, NAD+ may actually protect DNA, slow down aging, increase dopamine, support metabolism and restore function in neurodegenerative disease. It does this by supporting energy production and sirutins in each and every cell in the body. Whereas NAD+ depletion may be a root cause of aging, restoring NAD+ levels offers a way to undo the damage that results in chronic disease. NAD+ just may be a part of the elusive fountain of youth and one key to living a longer and healthier life.

References

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