I’ve reviewed a number of anti-aging compounds on my website, each contributing something different to fully optimized health.
But none have been as hyped up as nicotinamide adenine dinucleotide (NAD), even moreso than Metformin.
This tiny little molecule could possess the power to reverse the effects of aging and increase lifespan, according to many scientists hyping up its potential.
On the other hand, detractors are saying NAD is way over-hyped as a “fountain of youth” and we need many more clinical studies before we can think about using it.
As always, you’ll get the Jay Campbell answer to whether NAD+ is the next best thing in the field of anti-aging.
Or if we’re looking at a dud.
What Is NAD+?
Nicotinamide adenine dinucleotide (NAD+) is best known as a “co-enzyme”, which is a compound that binds to an enzyme and helps catalyze a chemical reaction within an organism.
It exists in two forms:
The pink molecule with blue letters represents nicotinamide, the pink molecule with black letters represents adenine, and the green molecule represents the ribose molecule. Each green + pink molecule together is considered a nucleotide, hence the name DInucleotide as they are joined together by a phosphate group.
“NAD+” represents the molecule in its oxidized form while “NADH” represents the molecule in its reduced form (i.e. with a hydrogen atom and two additional electrons)… you’ll see why this is important later.
The molecule has a rich history, dating all the way back to the start of the 20th century:
“NAD+ was first identified Sir Arthur Harden and William John Young in 1906 when the two aimed to better understand fermentation — in which yeast metabolize sugar and create alcohol and CO2. It took nearly 20 years for more NAD+ recognition, when Harden shared the 1929 Nobel Prize in Chemistry with Hans von Euler-Chelpin for their work on fermentation… The finding that fermentation, a metabolic process, relied on NAD+ foreshadowed what we now know about NAD+ playing a critical role in metabolic processes in humans.”
It wasn’t until the mid-2010s where NAD+’s presence in every living cell had a major purpose, and its popularity blew up almost overnight in the biohacking space:
“The NAD story took off toward the end of 2013 with a high-profile paper by Harvard’s David Sinclair and colleagues. Sinclair, recall, achieved fame in the mid-2000s for research on yeast and mice that suggested the red wine ingredient resveratrol mimics anti-aging effects of calorie restriction.
This time his lab made headlines by reporting that the mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN (nicotinamide mononucleotide), a molecule that naturally occurs in cells and, like NR [nicotinamide riboside], boosts levels of NAD”
And to nobody’s surprise, NAD+ is one of many molecules whose production in the human body decreases with age:
“…accumulating evidence indicates that a decrease in NAD+ levels contributes to the development of age-associated pathophysiology. The systemic NAD+ decrease is caused by both lowered rates of biosynthesis and increased use of NAD+.
The immense demand for NAD+ is caused by its importance in cellular oxidation–reduction reactions, including the majority of catabolic and anabolic reactions, such as glycolysis, fatty acid β-oxidation, tricarboxylic acid cycle, synthesis of fatty acids, cholesterol, steroids, etc.“
One study I was able to pull up shows just how rapidly the decline in NAD+ levels can be:
(Source – A is for males and B is for females)
This should be concerning to any aging biohacker as low NAD+ levels are linked to numerous health conditions such as depression, Alzheimer’s, mitochondrial dysfunction, and diabetes.
Surprisingly, the lifestyle habits needed to naturally increase NAD+ production are the same things needed to optimize mitochondrial health: Intermittent fasting, exercise, sleeping, lowering inflammation, avoiding alcohol, and more.
The Role Of NAD+ In The Human Body
In short, NAD+ is essential for the synthesis of the body’s main energy source — adenosine triphosphate (ATP).
It donates a hydrogen atom and two electrons to form NADH, and then those are used in separate biochemical processes to produce ATP:
There are three possible pathways through which NAD+ is synthesized before ATP synthesis happens:
To put all of the above in science terms for the geeks wanting to learn more:
“NAD+ is consumed in many catabolic pathways: in the cytosol, NAD+ is reduced to NADH by lactate dehydrogenase (LDH) during anaerobic glycolysis. In mitochondria, the three tricarboxylic acid cycle enzymes, isocitrate dehydrogenase (IDH), α-ketoglutarate dehydrogenase (α-KGDH), and malate dehydrogenase (MDH), reduce NAD+ to NADH. NADH serves as the primary source of reducing equivalents for complex I (NADH dehydrogenase) of the electron transport chain (ETC) to fuel OXPHOS, generating NAD+, ultimately reducing oxygen to H2O and producing ATP”
NAD+ also plays a vital role in antioxidant production to fight off the presence of reactive oxygen species (ROS):
“Of note, NAD+ deficiency exerts effects on the emergence of oxidative stress in multiple diseases, while boosting NAD+ has protective effects due to enhancement of antioxidant capacity via increasing the GSH levels and the activity of antioxidant enzymes. To counteract the detrimental effects of oxidants, cells can heighten the production of reducing equivalents such as NADPH. Moreover, NAD+-consuming enzymes, such as SIRT3, can also manipulate the cellular redox status via regulating the activity of enzymes for ROS generation and antioxidant factors for ROS eradication.”
One last mode of action worth noting is the activation of the SIRT-1 gene pathway, which then triggers mitochondria production while blocking mTOR activity directly and indirectly via AMPK (adenosine monophosphate-activated protein kinase) synthesis.
Not only does this make NAD+ a viable therapeutic target for treating SARS-CoV-2 (just ask Joe Rogan) and cellular senescence, but it also provides further insight into why the peptide 5-Amino 1MQ works to speed up fat breakdown while halting the growth of fat cells.
(Long story short: 5-Amino 1MQ inhibits the NNMT enzyme that converts nicotinamide into 1-methylnicotinamide, which allows nicotinamide to be converted into nicotinamide mononucleotide and then into NAD+ via the NAD salvage pathway)
With those three mechanisms in mind, let’s see how they apply to human health.
Top 4 Health Benefits Of NAD+
I won’t be able to summarize every single benefit of NAD+ as there are over 67,000 studies on this one molecule alone!
What I can do is briefly highlight what I believe will be the top uses for NAD+ in the anti-aging space if it ever reaches prominence in mainstream medicine.
NAD+ May Help Addicts Recover Faster
This came my way when I dug up an old Vice article about someone who used intravenous NAD+ therapy and noticed their mild cravings for alcohol had disappeared.
The idea is that high NAD+ doses exert a detoxification effect where the balance of neurotransmitters in your brain is restored.
It worked well for two anonymous addicts who had “deep” urges for hard drugs such as crack and heroin, but the benefits didn’t stop there.
According to an old FDA report published in mid-2019, several reports of NAD+ therapy alongside specific amino acids found the following addictions to be almost fully resolved:
- Compulsive gambling
The supposed protocol involves 0.8-1.8 g of NAD+ administered intravenously over 3-8 hours every day for 7-16 days straight, after which patients report a significant drop in withdrawal symptoms.
What’s surprising is how this protocol dates all the way back to the early 1960s yet remains an underground secret:
“IV treatment with NAD+ (diphosphopyridine nucleotide) resolved the cravings and withdrawal symptoms of individuals addicted to drugs and alcohol.
Depending on if these individuals experienced headaches and shortness of breath, NAD+ infusion ranged from 5 to 35 drops per minute.
Even intoxicated patients experienced immediate improvements, and two non-alcoholic individuals who received IV (and intramuscular) NAD+ before drinking alcohol had no hangover”
Some of the proposed mechanisms for why this happens include regulation of behavioral responses and lowered dopamine levels via increased adenosine levels.
NAD+ Is Promising For Alzheimer’s Patients
As I mentioned in the beginning of this article, the prevalence of Alzheimer’s disease is associated with lower NAD+ levels.
Which is why it’s fortunate to see promising results in animal studies:
“Pretreatment of neurons with NAD+ precursors protects against axonal degeneration following axotomy or even noise-induced hearing loss in mice, presenting a neuroprotection effect (Brown et al., 2014).
Moreover, induction of NAD+ levels after calorie restriction attenuated Aβ accumulation (Qin et al., 2006).
It is of interest that transgenic AD [Alzheimer’s disease] mice ameliorate memory loss by NR [nicotinamide riboside] treatment (Gong et al., 2013)”
The potential is there for both of the primary NAD+ precursors — NR (nicotinamide riboside) and NMN (nicotinamide mononucleotide) — especially with additional mechanisms such as repairing DNA damage and reducing neuroinflammation.
But the human clinical trials are sadly lacking because they are still in progress, slated to either finish in 2022 or start in 2022.
Most of them involve giving 300-1000 mg of NR per day for 8 weeks to either healthy patients, those with Parkinson’s/Alzheimer’s, or patients suffering from some form of cognitive impairment.
The therapy appears to be safe, so the only question left is whether increased NAD+ production will make a clinically meaningful difference.
NAD+ May Be Connected To Muscle Growth
Given the connection discussed earlier between NAD+ and the body recomposition peptide 5-Amino 1MQ, is it possible to see a positive effect on muscle growth?
One small human study in 2020 involving 13 overweight/obese men and women suggests so, as the results after taking 1000 mg of NR every day for 6 weeks led to a noticeable change:
“Markers of increased NAD+ synthesis—nicotinic acid adenine dinucleotide and methyl nicotinamide—were elevated in skeletal muscle after NR compared with placebo.
NR increased body fat-free mass (62.65% ± 2.49% compared with 61.32% ± 2.58% in NR and placebo, respectively; change: 1.34% ± 0.50%, P = 0.02) and increased sleeping metabolic rate.
…no effects of NR were found on insulin sensitivity, mitochondrial function, hepatic and intramyocellular lipid accumulation, cardiac energy status, cardiac ejection fraction, ambulatory blood pressure, plasma markers of inflammation, or energy metabolism”
NAD+ elevation may have to consistently take place for several weeks, as a separate human study lasting one week found that increasing NAD+ production did not make a difference:
“This study assessed the effect of 7-day NR supplementation on whole-body metabolism and exercise-induced mitochondrial biogenic signalling in skeletal muscle. Eight [20-something] male participants received 1 week of NR or cellulose placebo (PLA) supplementation (1000 mg day–1).
… There was no effect of NR supplementation on substrate utilisation at rest or during exercise or on skeletal muscle mitochondrial respiration. Global acetylation, auto-PARylation of poly ADP-ribose polymerase 1 (PARP1), acetylation of Tumour protein 53 (p53)Lys382 and Manganese superoxide dismutase (MnSOD)Lys122 were also unaffected by NR supplementation or exercise. NR supplementation did not increase skeletal muscle NAD+ concentration”
Fortunately, NR isn’t the only NAD+ promoting substance that works, as NMN will do the trick just as well.
“We administered 250 mg NMN per day to aged men for 6 or 12 weeks (n=21 for 6 weeks, n=10 for 12 weeks) in a placebo-controlled, randomized, double blind, parallel-group trial. Chronic supplementation with NMN was well tolerated and did not cause any significant deleterious effect.
Metabolomic analysis of whole blood demonstrated that the oral supplementation of NMN significantly increased the concentrations of NAD+ and NAD+ metabolites.
Moreover, NMN significantly improved muscle strength and performance, which were evaluated using the 30- second chair stand test, walking speed, and grip strength, and it showed no significant effect on body composition”
Here’s a deeper about how NAD+ is crucial for the maintenance of muscle strength:
“Skeletal muscle cells take in glucose and store it as glycogen. When there is a need for more energy within muscle fibers, glycogen is converted to glucose that is used to generate ATP. Skeletal muscle cells can contain thousands of mitochondria, which are where the aerobic/oxidative metabolism of glucose occurs.
As NAD+ is required as a hydrogen and electron acceptor and donor for aerobic cellular metabolism, NAD+ localization to mitochondria is important for muscle function. Mitochondria are the subcellular compartments that have the highest level of NAD+ in skeletal muscle cells.
However, 95% of the NADH in skeletal muscle is also localized to mitochondria. Therefore, the NAD+/NADH ratio is relatively low in skeletal muscle mitochondria despite there being high levels of NAD+”
In short, we have a useful tool for the aging athlete who doesn’t want to lose their physical power!
NAD+ Shows Other Avenues Of Optimizing Health
Some of the other possible use cases for NAD+ include (but are not limited to):
- Reversing the cognition-reducing effects of jet lag
- Treating diabetic nephropathy
- Combatting acute kidney injury
- Improving symptoms of chronic fatigue syndrome
- Lowering the risk of non-alcoholic fatty liver disease (NAFLD)
- Repairing impaired spermatogenesis
We need a lot more research in order to make more definitive claims, but we’re getting there!
The BEST Dose Of NAD+ For Better Health
With respect to the best NAD+ dose for the aspiring biohacker, it’s still the Wild Wild West as NAD+ is a “grey market” compound.
Here are the two protocols that consistently come up:
- Subcutaneous/intramuscular injection: 50-150 mg per day
- Intravenous therapy: 500-750 mg via IV drip over several hours, sometimes as much as 8 hours (and sometimes lasting several days)
I don’t recommend the oral supplements as the bioavailability for NAD+ is vastly inferior.
Ultimately, your choice of administration, dosage, and frequency of dosing will come down to numerous factors:
- The disease state you are treating
- The severity of your disease state
- Any side effects you experience with a given dosage, frequency of dosing and/or method of dosing
- Your financial budget
This is brand new stuff, so venture bravely and use common sense
There is one method of the IV drip that shortens the administration time to 10 minutes, and Ben Greenfield refers to this as “push IV”.
Again, this is entirely up to you.
If you feel more comfortable under the guidance of a clinic that’s done this thousands of times successfully, be prepared to pony up the extra cash.
If you’d rather self-experiment and inject yourself without any supervision, you’re responsible for figuring out what’s safe and effective.
Side Effects & Safety Profile Of NAD+
Some of the most commonly reported NAD+ side effects include:
- Upset stomach
- Hot flashes
Most people get used to the side effects as long as they are not overdosing or administering the solution too fast.
While the injections haven’t been well-studied, the oral formulations appear to be safe and tolerable in human trials when given at high doses for several weeks.
The absolute youngest you should be using NAD+ to have any real benefit is 30, and even then most people recommend holding off until their late 30s or early 40s.
Finally, there is one thing you should absolutely do if you use NAD+: Use betaine (trimethyl glycerine, a.ka. TMG) concurrently.
This recommendation comes because of the methylation that happens to NAD+ …
“Methylation is the transfer of a methyl group (one carbon and three hydrogens) from one molecule to another in the body and is a fundamental element of our biochemistry. Methylation is accomplished by enzymes.
Methylation can modify heavy metals, regulate gene expression, RNA processing and protein function. It is recognized as a key process underlying Epigenetics. Epigenetics involves essentially turning on and off switches of different genes.”
The process of methylation isn’t a bad thing except when it gets out of hand…
” The process of metabolizing NAD+ stresses the body’s “methyl pool,” the molecules that donate methyl groups. The methyl pool is crucial to maintain one’s health.
A methyl group needs to be added to NAD+ to create MeNAM, which uses up methyl groups that are needed for other biochemical reactions. If adequate amounts of methyl groups are not available than methylation is diminished allowing genes to either be kept on or off sometimes resulting in significant problems.”
“Also, when NAD+ treatments are given, as the NAD+ is metabolized it is converted into a compound called Methionine which is ultimately converted into a compound called Homocysteine. Homocysteine is a byproduct of methionine metabolism. It is a powerful pro-oxidant and free-radical generator known to be a leading cause of heart disease and other problems“
To make matters worse, some people have a genetic defect that exacerbates the problem:
“Many U.S. adults – some estimates are as high as 60 percent – have a genetic defect in a critical enzyme involved in methylation – MTHFR.
MTHFR is the enzyme that creates active folate from inactive folic acid obtained from food and supplements. Individuals with this genetic defect can have a significantly decreased methylation abilities.
This situation can result in an increase in the undesirable amino acid metabolite homocysteine”
The best course of action is to take 1000 mg of betaine alongside NAD+.
Not only does it take care of the short-term and long-term side effects, but it’s also dirt cheap and it helps replenish the “methyl pool”.
How To Buy Pharma-Grade NAD+ Online
If you buy NAD+ by visiting a medical clinic for an IV drip, expect to pay several hundreds of dollars per injection.
And with IV treatments lasting a few days to a few weeks, what you’re paying isn’t proportionate to the return on investment you’re looking for.
So the best course of action is to find a reliable peptides supplier who will sell injectable NAD+ to you for a reasonable price.
But be wary of a few things…
First, make sure you know EXACTLY what is in the vial.
NAD+ is highly soluble in water up to a maximum concentration of ~175 mg/mL.
Which means if you get NAD+ as a lyophilized powder, you have to add the appropriate amount of bacteriostatic water or else it won’t fully dissolve (i.e. you did not add enough water and now the solution is oversaturated).
So to compensate for this, some manufacturers add a “buffer” to allow more NAD+ to dissolvein the water.
Second, be aware of possible side effects associated with the use of a buffer.
This is an N-of-1 thing, but my business partner Nick Andrews personally has had horrible headaches that come from the use of a buffer.
Maybe it will happen to you, maybe it won’t… but just be aware it could happen.
Now… onto where you should buy NAD+.
From Limitless, it’s a manageable price.
Limitless Life Nootropics and Nick have collaborated to stock the purest, highest-concentrated NAD+ you will find in the world!
Use code JAY15 to get 15% off your order!
And just to make the deal sweeter, you can get NAD+ in one of two forms.
The lyophilized version of NAD+ is vacuum-sealed, micro-filtered for impurities, and comes shipped with a dry ice pack.
Keep it in the fridge for short-term storage, and frozen and vacuum-sealed if you want to store it long-term (good at room temperature for six months, good for a few years if stored long-term).
The pre-liquified version of NAD+ comes ready to go with the ice pack and is shipped frozen.
For maximum potency, you want to use it within 24-48 hours of receiving it… although you can stick it in the freeze and defrost it when you are ready to use it.
With either choice, limit the amount of freeze-thaw cycles to maintain maximum purity/stability of the product.
Both products come with a waterproof label that says “Limitless Longevity”.
Nothing to worry about, just a rebranding for supplements being launched in the future.
Additional Reading Resources For NAD+
There’s not much to say about NAD+’s health benefit as its full potential is yet to be unlocked.
Your best course of action is to visit a clinic well-experienced in offering NAD+, get an idea of what it can and can’t do for you, and then decide if you want the IV drip or an injection.
Raise Your Vibration To Optimize Your Love Creation!
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