Whatever your goals in life, two benefits are almost universally appreciated by everyone: 1) having more energy and; 2) slowing down aging.
And whenever there's a compound that promises those two benefits, it will create a crazy hype in the health and biohacking community.
In this case, two compounds called "nicotinamide riboside" and "nicotinamide mononucleotide" created such interest due to their purported ability to achieve these benefits.
Both compounds are different versions of vitamin B3 or "niacin".
But due to the promised benefits, many people began taking does that are 50-300 times as high as the Recommended Daily Allowance.
The science on these compounds, however, is fairly recent and far from settled, and it's safe to question whether taking such huge doses is a smart thing to do. Additionally, you could question whether these compounds achieve what they promise.
So I decided to explore the justification behind these supplements. Does the hype live up to reality?
Let's find out!
To start things off, let me give you my overview of this blog post:
Want to know the full story?
Let's get started:
Before considering what NAD+ does and why it's important, let's take a quick detour. Again, NAD+ may help you slow aging and up your energy levels. The detour helps you understand the role of NAD+ later on:
Every complex biological organism on this planet is made up of billions if not trillions of cells. Cells are the "basic unit of account" that make up complex life.
One theory about the creation of life on this planet is that very simple cells like bacteria and Archaea "fused", which then allowed for a "division of labor" within each cell. Of course other theories exist on this subject, but let's, for now, run with this theory (1; 2).
The division of labor within a cell subsequently allowed for an excess of energy and more complex organisms to arise.
As a result, what makes a very complex human being and a very simple organism different is the co-existence of billions or trillions of cells, versus just a few. By many cells working together life could thus develop into ever more complex entities.
Every single organism and cell needs energy to exist (3; 4). In other words, without energy you would die very quickly.
NAD+ comes in wherever energy plays a role. NAD+ is both central to energy production as well as cell signalling (5; 6; 7). Cell signalling is the "information" part of the equation as opposed to that of "energy" - "information" plays a lesser role in this blog post.
The problem is that NAD+ levels decline with age (8; 9). With age, those declining NAD+ levels also lead to a decline in energy production.
That decrease in energy production subsequently sets you up for many health conditions, such as diabetes, heart and blood vessel diseases, cancer, and problems with the nervous system (8; 9).
Lower NAD+ levels may also be one of the reasons why you're simply less "lively" once you're 80 or 90 years old.
Through niacin supplementation, anti-aging theories claim that increasing NAD+ levels may lower your risk for metabolic and neurodegenerative conditions, as well as increase your healthy lifespan - or "healthspan".
More daring claims make you believe that you can feel and behave like 18 or 25 again. While I'm only later considering whether that claim is true, let's first look at how such claims can be scrutinized.
To understand NAD+, you need to learn about energy creation in the cell:
Most kids in elementary school already know that you need both oxygen and food to survive. But what most adults don't even know, however, is that the oxygen and food are directly processed by your "mitochondria".
Mitochondria are the "energy-producing factories" of your cells--although they also fulfill other roles such as helping your immune system (10; 11; 12).
The consequence is that the better your mitochondria function, and the more mitochondria you have, the healthier you'll generally be.
The oxygen you're breathing and food that's broken down in the digestive system thus eventually ends up in your cells and is primarily processed by your mitochondria (13; 14). In plain English, when you're eating fats or carbohydrates, their carbon molecules are used to produce energy.
On the one hand, that process of breaking down is chemically and physically very complex and not even fully understood. On the other hand, what is known, is that NAD+ plays a vital role in that process of creating energy (15; 16; 17).
So once your NAD levels deteriorate, it's harder to stave off disease and to follow an exciting lifestyle.
Declining NAD+ levels are thus one of the reasons why your grandmother needs to take afternoon naps. It's also the reason she doesn't go dancing in the middle of the night anymore.
NAD+ can be created from different sources, such as vitamin B3 as well as from proteins in your food.
Proteins can be broken up into amino acids, and one of these amino acids can support your cells NAD+ levels. That amino acid is called "tryptophan" (18; 19).
Using these nutrients, NAD+ is produced in different parts of the body, such as (predominantly) the liver, your gut, small amounts in other organs, and in individual cells throughout the body (20; 21).
A currently predominant scientific theory holds that taking very high doses of either vitamin B3 or tryptophan will improve your body's NAD+ production, thereby lowering the effects aging has on your body.
The assumption, again, is that as a 70-year-old you'll return to your youthful energy levels.
You may think: "but how do you exactly know for sure that lower NAD+ levels are the cause of aging?"
That's a great question.
Very strong evidence actually exists that NAD+ deficiency is directly responsible for some of the "side-effects" of aging, such as lower energy levels and metabolic disorders such as diabetes (22; 23; 24).
Boosting NAD+ sometimes also reverses the impact of the aging process. Furthermore, niacin is the most important way in which you can improve those NAD+ levels. So the next logical step is to look at different types of niacin you can take:
There's no such thing as a "nutrient" - which is true for niacin as well. Just like different types of magnesium, iron, vitamin B12, and vitamin K exist, the same is true for niacin.
In fact, four main niacin types can be found on the market today:
All of these are eventually converted into NAD+, albeit, all in different ways. Some of these types - such as nicotinic acid - require more intermediary biochemical steps to be converted while others are processed more straightforwardly.
Let's explore all four types below:
Again, nicotinamide is mainly animal food-based (76; 77). Nicotinamide is converted into NAD+ by requiring magnesium and ATP.
Most plant foods only contain a fifth to a tenth of the nicotinamide as animal foods do, and thus, animal foods are the best nicotinamide source.
Additionally, nicotinamide does not cause "flushing", the redness in the skin associated with taking high doses of "nicotinic acid", the next niacin form:
Nicotinic acid is the "plant-based" form of vitamin B3 (90; 91).
In the small intestine, the part of the digestive system that follows the stomach, that nicotinic acid is converted into nicotinamide. Hence, the predominantly plant form of vitamin B3 needs to be converted into the "animal form" to be used.
For that conversion process, additional nutrients such as potassium are required. Plant foods are generally a great potassium source, so there should be a problem for proper conversion.
So unlike carotenes, which are "plant versions of vitamin A" that are sometimes poorly converted by the human body into usable forms, the same is most likely not true for nicotinic acid.
Different subtypes of nicotinic acid also exist:
You may know of nicotinic acid from the Niacin detox protocol. I've extensively tested that protocol on myself as well.
"Niacin flush" means that you're experiencing (possible extreme) redness and blood flow in the skin.
Now, contrary to popular belief, the niacin flush is not fully benign. In fact, the niacin flush is an inflammatory reaction involving "prostaglandins" (97; 98; 99). That niacin flush can be blocked by taking anti-inflammatory drugs such as ibuprofen, although that's generally not a smart thing to do.
And there's another reason why a niacin flush is not fully benign:
The body binds excess nicotinamide to glycine if it cannot be converted into NAD+. If that process of binding to glycine fails, the body produces a "flushing response" (93). Glycine is yet another amino acid - a building block of protein.
Once you deplete that glycine, you'll lower your health. Most people also consume too little glycine because they don't include bone broth, gelatin, or collagen in their diets.
In general, there are no "positive gains" to be made by creating a massive niacin flush. Quite on the contrary, a niacin flush is probably a sign that you've taken too much of this vitamin and are now experiencing overdose symptoms.
Fortunately, science has developed "sustained" and "extended" release versions of niacin. Are these forms any better? Let's find out:
The sustained and extended-release forms of nicotinic acids do not produce a flush, simply because your methylation pathways of the body can more adequately process this niacin.
"Niaspan" is an example of extended-release niacin.
Due to more adverse effects such as liver damage, extended-release versions may be even more dangerous. I think one reason for this outcome may be that the methylation pathways are not continually overloaded, leading to, paradoxically, better health outcomes.
The sustained release can be used though, although it's easy to overdo. In general, I recommend the flush "instant" version as safest, and the sustained version as a second option of nicotinic acid.
Don't use the extended-release. Next, there's the first niacin many use for anti-aging purposes (although regular niacins also help in that area):
Nicotinamide Riboside (NR) is one of the newest kids on the block (94). NR has received quite some attention in the biohacking and anti-aging circles.
In nature, NR is mostly found in tiny quantities in milk. But because you can buy this niacin version as an isolated compound online, it's now possible to take much more NR than you'll ever get from food.
This type of niacin has "ribose" added to it, from which the name is derived.
NR mostly goes to the liver to create NAD+. Then the liver sends nicotinamide to the rest of the tissues. NR can be stored in the liver, unlike other forms such as NMN. For that reason, NR has the advantage of lowering the body's taxation of the methylation pathways.
NR gives a better NAD response than simple nicotinamide supplementation. Why? Again, excess NR is not immediately expelled like nicotinic acid, potentially creating more NAD+ in the liver.
What's interesting is that NR cannot into the brain, not even intravenously (through injection). Nicotinamide, on the contrary, can though. Almost all tissues can benefit from NR though, fortunately.
I'll state more the science of NR in a later section.
Nicotinamide Mononucleotide (NMN) is another supplemental niacin type that's gotten really popular.
Do good reasons exist for supplementing with this form though? Hardly: NMN isn't absorbed intact in the gastrointestinal tract, and is most likely converted straight into to nicotinic acid. (96).
Other, more recent studies, do show that NMN might be absorbed intact (95).
Most people use NMN because it is a more direct precursor to NAD+ than nicotinamide. The problem, however, is that some evidence currently exists that this compound is converted into NAD+ if taken orally.
NMN converts into NAD+ by adding a compound called "AMP" (95)
As with converting nicotinic acid, conversion of NMN into NAD+ requires magnesium and potassium. Supplements that don't contain enough magnesium won't therefore optimally work for boosting NAD+ (if you're magnesium deficient like so many people).
Sublingual Nicotinamide Mononucleotide
Many people online swear by using NMN under the tongue. Research on this topic is sparse, however.
As of this time, I don't recommend this supplementation type - I'm not convinced that NMN can enter the cell directly in its specific form, so taking the compound under the tongue wouldn't solve the fundamental issue.
Let's lastly look at how niacin and it's downstream compound NAD+ create energy in your mitochondria:
NAD+ is an electron acceptor, thereby easily gaining electrons from the food you eat. The carbon units from carbohydrates and fats can donate electrons which then help your mitochondria create energy.
Without electrons from food (or body fat), your body cannot survive long-term. Due to the specific role of NAD+ in energy creation, it plays a fundamental role in (preventing) the aging process.
Again, the more energy your body can process, the better it functions and the longer you'll stay young.
It's not just NAD+ that matters though--NAD+ relates to other compounds such as NADH and NADPH.
I'll briefly mention NADH and NADPH here to show you that niacin does not just concern NAD+ creation. Niacin can thus have more far-reaching effects on your health than just boosting NAD+:
Niacin can also be converted into NADH. NADH is similar to NAD+ and just has a hydrogen molecule added to it, as well as two electrons.
The "+" sign regarding NAD+ means that it's an electron acceptor (i.e. NAD+ is oxidized). NADH has accepted these electrons and has become another compound in the process.
Just like NAD+, NADP also plays a role in the energy-producing process in your mitochondria.
NADPH is made from NAD+. Compared to NADH, NADPH has one added phosphate group. Some of the NADPH roles are:
NADPH is mostly responsible for anabolic processes. Anabolic processes build up tissues. NAD+ and NADH, on the contrary, are responsible for catabolic processes. Catabolism means breaking something down, and NAD+ and NADH help you break down the constituents of food in the mitochondria.
The big picture? Observe that NADH and NADPH are also involved with energy production and the aging process - and, again, are both created from niacin.
So hopefully you now understand that NAD+ is not the only downstream substance affected by niacin, even though it's the most talked-about one.
To gain a deeper understanding of NAD+, moreover, you also need to learn about the role of niacin in the human body:
In this section, I'll explain why niacin is essential to your health.
Being a vitamin, niacin or vitamin B3 needs to be consumed for you to live (long-term). Survival with less niacin in your diet is possible, but eventually, without niacin, you'll die.
And because vitamin B3 is a water-soluble vitamin, you need to consume it relatively frequently - on a daily basis if possible - because the vitamin cannot be stored like fat-soluble ones.
As you can see, niacin is quite important for many functions in the human body:
Of course, as I've already mentioned when talking about the niacin flush and methyl group depletion, more niacin is not necessarily better.
So let's also look at a few other possible side-effects resulting from too much niacin:
As you can see, taking 5,000 milligrams of niacin each day instead of 50 milligrams (which already exceeds the Daily Recommended Allowance significantly, is not always a smart move.
You cannot supplement with high niacin doses blindly. More is not (always) better.
If you are going to use higher niacin dosages for long periods of time, you'd better be sure to know what you're doing.
Of course, less is not better either:
Pellagra - a skin condition among others - is one of the most important symptoms of niacin deficiency. With Pellagra, sunlight exposure becomes really problematic because NAD+ cannot protect you against the DNA damage of the ultraviolet light.
If you don't get lots of sunlight exposure, however, the skin symptoms may not appear while you still suffer from the metabolic and neurodegenerative problems (78).
The condition may also be underdiagnose, especially in the developing world (82; 83).
With less severe niacin deficiency, you can get mental health issues, psychiatric problems, low energy, trouble losing fat, an inability to tolerate cold, and more. Niacin deficiency is no fun, although it's also (very) rare in developed countries today.
In a later section, I'll tell you why most people actually have decent niacin status.
And now that you understand the role of niacin, let's look at the benefits of optimizing your NAD+ levels:
I'm this section I'll specifically look at why you want higher NAD+ levels.
Recall that many people are taking high NMN and NR doses for the specific purpose of boosting NAD+.
Higher NAD+ levels- accomplished through supplementing with niacin (in different forms) - has the following benefits:
As you can see, many reasons exist why you would want to boost your NAD+ levels. It's thus not weird that people are supplementing with variations of niacin to improve their NAD+ levels.
Young chickens at my farm: these have very high NAD+ levels because they're young, leading to years of successful foraging!
Let's next take a look at why you'll want to avoid low NAD+ levels. One last section of doom and gloom:
The end result of having low NAD+ levels are naturally the opposite of having higher levels. So let's look at what happens if you've got lower NAD+ levels in your mitochondria:
(I won't cover these topics in extreme detail because they're basically the opposite state of having high NAD+ levels.)
Now that you understand the basics regarding both niacin and the effects of low and high NAD+, let's look at getting your niacin needs met through food.
And if you want to skip the food section, then the next 7th section considers the topic of supplements.
In the next section, I'll briefly talk about getting your niacin through food.
The upside is that most people get adequate niacin from their diets to prevent a deficiency. The downside is that food is never going to supply the levels of NMN or NR that you find in most supplements.
To be clear: it's easy to consume 20 milligrams of niacin through food on a day, or even 50 milligrams. Consuming 2,500 milligrams through food alone, however, is impossible.
This section thus also helps you understand that what most people do with NMN or NR supplements is unprecedented.
By taking 250 milligrams of NR, you're not just supplementing but you're taking supra-physiological doses (doses much greater than normally found in the body) that cannot be recreated through a diet.
So let's look at the best niacin-rich foods out there.
Below I've listed the top 50 foods that are high in niacin. A few pointers though:
So without further ado, the top-50 list of best niacin food sources, per 100 grams (3.4 oz) of food (141):
Next, let's consider the foods that have the worst niacin levels:
In most plant foods, niacin is only available with proper preparation. This topic ventures beyond the scope of what I'm trying to achieve in this blog post, but, you can generally assume that niacin only becomes fully available with soaking/fermenting/sprouting.
No need to worry though if you eat some meat.
(Want to learn more about why eating meat is healthy? Read my blog post on why vegetarian and vegan diets end up in disaster).
Smoked BBQ brisket: heavenly taste and great niacin source -
for boosting my NAD+ levels, of course ;)
The Daily Recommended Allowance for niacin is about 15 milligrams, but indications exist that this number is too low on a relative basis - especially for women (84; 85). With certain conditions and genetic mutations, you may also need more niacin (86; 87; 88).
Fortunately, 3.4 ounces (100 grams) of red meat, pork, or fowl already supplies 10 milligrams of nicotinamide, making it nearly impossible to under-consume. Consuming 4-8 ounces of meats each day alone will thus ensure that you're getting sufficient niacin through your diet.
In the US, most men consume 28 milligrams of niacin each day while women get 18 milligrams (145). Refined grains that are fortified with niacin do heavily contribute in that case though.
If you want a more precise calculation then use the following: it's recommended to consume about 1.6 milligrams of niacin per 250 kcal each day (146). More precise calculation exist as well, but because most people are not niacin deficient, I'll move to the next topic.
Additionally, there's another method to up your niacin intake:
Breaking down protein into niacin is possible by breaking down an "amino acid" called "tryptophan 'from your food.
Amino acids are building blocks of proteins. The possibility to convert niacin from protein is only possible if you've got an excess of protein in your diet though.
So if you're not eating much protein, or if you're working construction all day and need protein for recovery, very little if any tryptophan is going to be converted into niacin (89).
If you've got a desk job and you're eating 150 grams of protein a day at a 70 kilogram (~155 pounds) body weight, however, your protein intake will contribute to your niacin intake.
The process of converting tryptophan into niacin is more metabolically expensive though, and requires more other nutrients in your diet to be allocated towards niacin production. So if possible, it's best to get niacin directly through your food.
Niacin needs are not the same for everyone. In certain circumstances, you can expect your needs to be higher. Examples are if you're:
Currently, there are no very precise lab tests for niacin status on the market.
(If you're interested, an organic acid test or methylated niacin may both give independent information that can be useful about your status).
A better idea than lab tests? Have a good animal protein intake for both niacin and tryptophan, which is really easy.
The next step is to look at how taking high niacin doses (250 - 5,000 milligrams) affect your body's physiology:
The moment you've been waiting for: supplementing with high doses of niacin, such as nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN).
So let's get started and look at the science of NAD+ boosters.
I'll look at the specific benefits of different types of niacin, and their potency for exhibiting anti-aging benefits as well as improving your energy levels. Below I've listed the effects of these NAD+ boosters according to different studies:
Let's start with the benefits of NR:
The upside: nicotinamide riboside is clearly doing something in the body.
So despite the relative lack of research on this compound, it may be a good tool to boost NAD+ levels.
Again, NR is mainly found in milk (but yeast and beer are more uncommonly consumed sources) (171). Higher levels of NR can only be consumed through supplements, and although the compound is similar to nicotinamide, it probably has superior effects.
First of all, very few (high-quality) NMN studies are currently published.
Most of the published studies concern animals--I haven't found any in humans. Whether NMN works thus remains to be seen.
Questions also exist whether NMN can enter cells intact. If not, NMN would boost NAD+ levels only indirectly, and not as NMN but as a different compound (probably another niacin form).
And yet, looking at reviews online, the effects of NMN on overall health are very promising. Let's thus look at a few studies in relation to NMN:
The bottom line is that NMN:
Hence, I do not recommend using nicotinamide mononucleotide as of right now, and prefer nicotinamide riboside.
Then, there are possible side-effects of using higher doses of NAD+ promoters such as NR and NMN:
The list of potential side-effects of supplementing with NMN and NR should steer 90%+ people away from taking large 250 - 5,000 milligram daily doses. These compounds are not benign.
This also supports the conclusion from the NeuroHacker formulators who decided not to include high doses of NR or NMN in their new anti-aging and anti-stress formula Eternus.
Their statement on the topic reads: (You can read the full statement on their website HERE)
Nicotinamide riboside and nicotinamide mononucleotide are newer (and very expensive) dietary ingredients used to boost NAD+. The niacin equivalents—niacin (nicotinic acid; NA) and niacinamide (NAM)—boost NAD+. L-tryptophan is also a precursor for NAD+. We included both NA and NAM, as well as L-tryptophan in our Eternus formula, because these ingredients can be used to make NAD+ and this approach supports three different ways of making it. Redundancy is a core value within complex systems science and something we look for when formulating our products.
Right now, the best supplements seem nicotinic acid (NA), niacinamide (NAM), and nicotinamide riboside (NR).
Much more research is needed to find the true standout of the three.
Some indications exist that NR is more easily stored in the liver, without needing immediate conversion into NAD+ or to be excreted.
Nicotinamide Mononucleotide (NMN) looks like a different version that may or may not be able to deliver good results, despite its high price.
I'm leaning slightly towards NR at this point, although much more research is needed and all forms do look promising.
If you do decide to use these niacin forms, especially the nicotinamide riboside which may have the biggest potential benefits, I recommend following this strategy:
There's one more option I want to mention in this blog post though:
Some people have now been injecting NAD+ directly into the bloodstream. Just to be clear, these people are not injecting niacin into the bloodstream but NAD+.
You can watch a video of Ben Greenfield doing so right HERE. The process is quite burdensome and can actually be somewhat painful.
The reason is that injecting NAD+ directly into the bloodstream may activate the immune response. Extracellular NAD+ may function as a sign of stress, and thus, might not or won't have the benefits of improving NAD+ levels through regular food or supplementation.
Additionally, no studies have currently been published on the effects of injecting NAD+.
And even if such studies were published, however, the long-term consequences of that action would be unknown.
There's thus no way to know whether injecting NAD+ contributes to your health, or detracts from it - and such knowledge is not expected to be available in the next few decades either.
Moreover, in the past, strategies that use great amounts of a certain nutrient - called "supraphysiological doses" - have been sub-par in their results. Very high doses of vitamin C don't make your immune system work any more efficiently, for instance, and taking lots of antioxidants can even detract from your health because they impede your workout gains (150; 151; 152; 153; 154).
In other words, directly injecting NAD+ into your blood may have unintended consequences that science is currently unaware of. I, therefore, do not suggest you inject yourself with NAD+ as of right now. And if you decide to do so, always consult a physician.
So now that injections are out of the window, let's look at the best supplement:
So, want to take supplements to boost your NAD+? In that case, you might as well take the best on the market:
Tru Niagen Nicotinamide Riboside
The company selling that NR is very reputable and 500+ reviews are almost all happy with the product. Of course, NR is pricey, but that's the price you pay for cutting-edge technology.
Another option is NeuroHackers 'Eternus'. The tagline of this supplement reads 'Supports cell energy for better aging'.
Though the formulation of this supplement is not focused soley on niacin (it does contain 100mg of niacinamide and 25mg of nicotinic acid per serve), it does also contain a range of ingredients that are supportive of increasing NAD+.
I have not used Eternus for long enough share include personal experiences, but I have had great results with their cognitive boosting formula Qualia Mind (read more about that HERE) so I am confident that this new product will work well.
Like Niagen, Eternus is a premium product and not for everyone (though discount code FERGUS will knock 15% off the price) but if someone is looking for an anti-aging supplement that doesn't soley relay on niacin then it is worth considering.
If you're on a tight budget and want to boost your NAD+ levels anyway, I recommend a pure niacinamide powder (though make sure you purchase some micro-scales and be very careful with your measurements!)
Again, make sure to apply all the strategies in this blog post to make sure you're using higher doses of niacin safely.
If you're not replenishing methyl donors, you can expect side-effects after some time of use - as many reviews on the internet attest to.
Additionally, recall that high doses of niacin have not been studied in great detail yet, especially the long-term effects. What effects are to be expected cannot be conclusively be told yet.
Want another option than supplementing? In that case, let's look at a few strategies you can employ to naturally improve your NAD+ levels:
Who would have thought that lifestyle strategies have a huge impact on your NAD+ levels? let's look at a few areas:
As you can see, lifestyle interventions will almost certainly increase your NAD+ levels. So if you're living in a polluted city, you don't exercise a few times a month, and you don't breathe properly, then there's no reason to take nicotinamide riboside or nicotinic acid.
Get your lifestyle in order first, and only then supplement.
Still my favorite way to boost NAD+ levels. Follow me on Instagram by the way.
Contrary to my initial expectations, there is "something to" high doses of niacin.
Many studies investigating forms of niacin such as nicotinamide riboside look promising in the results they get.
And yet, I'm not yet willing to recommend full-blown supplementation with this compound, especially if your lifestyle is not yet in order.
If you're living in a city with lots of air pollution, not exercising, eating poorly, and not sleeping well, you probably need to steer clear from supplementing with NMN or NR. In that case, you're just missing the elephant int he room.
And yet, with many studies coming out on this topic in the last few years, I do think the coming decades will be very promising with regard to niacin.
Some of the top-notch anti-aging researchers in the world, such as David Sinclair -- who brought the compound "resveratrol" into the public consciousness more than a decade ago -- is very much into promoting the role of NAD+ now.
And yet, you should be wary of too much hype around anti-aging promises. The resveratrol supplement he promoted as adding decades to your life 10 years ago has turned out a meager compound that perhaps increases blood flow and helps your body store sugars in muscle cells instead of fat cells.
I'll wait to see how this high-dose niacin thing turns out. Seeing is believing.
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