NAD+: Why nicotinamide riboside is better than NMN

Fountain of youth in pill format? The prospect of halting the ageing process with a simple dietary supplement fascinates researchers and health enthusiasts alike. At the center of modern longevity research is a small molecule called NAD+ (nicotinamide adenine dinucleotide). NAD+ is not a mysterious elixir, but an essential coenzyme that is involved in almost all important metabolic processes in our cells. However, NAD+ stores are not inexhaustible: with increasing age, the NAD+ level in many tissues decreases【1】. Some scientists even suspect that NAD+ levels are significantly lower in middle age than in youth - a possible driver of why we age in the first place. (The links between NAD+ levels and ageing processes have not yet been confirmed by the EFSA; further studies are required).

At the same time, there is growing hope of compensating for this age-related loss of NAD+. This is where special NAD+ precursors come into play - substances that are supposed to raise NAD+ levels again. Two candidates in particular are causing a stir: nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR). Both are precursors of NAD+ and are considered to be promising anti-ageing substances. Even prominent age researchers such as Dr. David Sinclair from Harvard Medical School are experimenting with them and integrating NAD+ precursors into their personal programs. But which of these molecules is the more efficient upgrade for our cells? In this article, we take a deep dive into the science and explain how NAD+ works, how NMN and nicotinamide riboside differ and why nicotinamide riboside is the favored NAD+ booster according to current research.

What is NAD+? - Fuel of the cells and guardian of repair

To understand the importance of NAD+ for longevity, let's first look at what NAD+ does in your body. The abbreviation stands for nicotinamide adenine dinucleotide - a molecule that is found in every cell. Think of it like a battery that carries energy back and forth between cell reactions. NAD+ constantly oscillates between two forms: NAD+ (uncharged) and NADH (charged with an electron). When nutrients (e.g. glucose or fatty acids) are burned, NAD+ takes up electrons and becomes NADH. NADH then releases these electrons again in the mitochondria - the "power plants" of the cell - to produce ATP (the universal energy carrier). Through this cycle, NAD+ is centrally involved in energy production. No NAD+ = no ATP = no life. Consequently, a drop in NAD+ levels leads to lower cellular energy production - which in humans can manifest itself in fatigue and reduced physical performance, for example. (The links between NAD+ levels and fatigue and reduced performance are not currently confirmed by EFSA; further studies are needed). Interestingly, vitamin B3 (niacin) is a precursor of NAD+. In the European Union, it is an approved health claim that niacin contributes to normal energy metabolism and helps to reduce tiredness and fatigue - which impressively underlines the fundamental role of NAD+ in our metabolism.

But NAD+ can do more than just provide energy. As a signaling molecule, it activates a number of enzymes that are responsible for cell repair and adaptation to stress. Particularly important here are the sirtuins, often known as "longevity genes". Sirtuins are enzymes that use NAD+ as fuel to regulate DNA repair, anti-inflammation and metabolism, among other things【4】. Put simply, sufficient NAD+ enables sirtuins to repair defective areas in the genome and keep the cell balance in equilibrium - processes that could keep us healthy for longer. In addition, PARP enzymes (responsible for DNA repair) and CD38 (an enzyme of the immune system) also consume NAD+. Unfortunately, it is precisely these NAD+ consumers that become more active with age: DNA damage increases, inflammatory reactions increase - and with them the consumption of NAD+【4】. The result is a vicious circle: less NAD+ means less repair capacity, which in turn could (theoretically) lead to faster ageing at the cellular level. A much-noticed study on mice in 2013 impressively showed how strong this mechanism can be: Older mice had drastically reduced NAD+ levels and showed signs of "cellular pseudohypoxia" - their mitochondria received the signal as if there was a lack of oxygen and shut down energy production【2】. However, when the researchers gave the old mice an NAD+ precursor, cell metabolism returned to normal and resembled that of young animals【2】. In other words, by replenishing NAD+, the cells of the aged mice appeared to regain some of their youthfulness. (The links between NAD+ precursors and potential "rejuvenation effects" are currently not confirmed by EFSA; further studies are needed). This finding laid the foundation for the hype surrounding NAD+ precursors in anti-ageing medicine.

NAD+ and ageing: does a higher level promise rejuvenation?

The idea is tantalizingly simple: if ageing is associated with declining NAD+ levels, could high NAD+ levels protect against ageing? Several studies on model organisms point in exactly this direction【4】. In nematodes, mice and rats, researchers have observed positive effects on age-related conditions by increasing NAD+ levels【4】. One example: in mice, the additional administration of NAD+ precursors led to improved mitochondrial function and a revitalization of stem cells, which are important for tissue regeneration【4】. A study from 2016 (Zhang et al.) showed that old mice that received nicotinamide riboside via the diet had less muscle atrophy and lived longer than untreated mice【1】. The lifespan of the animals increased by a significant percentage, proving that an increase in NAD+ levels canhave an anti-ageing effect【1】. (The links between increased NAD+ levels and a longer lifespan have not yet been confirmed by the EFSA; further studies are required). However, it is important to note that mice are not humans. What works in animal models must first be proven in clinical studies on humans. Nevertheless, such results have caused quite a stir. NAD+ became a hot candidate in the hunt for the fountain of youth, and dietary supplementation with NAD+ precursors became a trend.

Before we go into the details of the available NAD+ precursors, we should briefly clarify how your body produces NAD+ in the first place. In principle, there are two sources: Food and your own cellular production. Vitamin B3 (niacin) from food - such as meat, fish, whole grains or mushrooms - can be converted into NAD+ in the body. The amino acid tryptophan (from protein-rich foods, for example) can also lead to NAD+ via a multi-stage process. These sources cover your basic requirements and prevent deficiency diseases. However, the basic level of NAD+ may not be sufficient for optimal function in old age (or in stressful situations)【4】. Although the body has its own recycling programs to restore depleted NAD+ (keyword: salvage pathway), under constant stress - whether due to overeating, inflammation or simply the passing years - bottlenecks apparently occur. This is where NAD+ precursors come in: They are supposed to provide extra "building material" so that the cells can produce more NAD+ than would be possible through normal nutrition alone.

NAD+ precursors: Which ones are there and how do they work?

• Nicotinic acid (niacin): Classic vitamin B3, known for decades. Niacin can be converted to NAD+ in the body and has approved health claims, for example it helps to reduce tiredness. However, nicotinic acid in higher doses often causes the infamous "flush" - an unpleasant reddening of the skin with a feeling of heat.
• Nicotinamide (niacinamide): The amidated form of niacin, also a vitamin B3 classic. It is tolerated without flushing and can build up NAD+. However, studies show that very high doses of nicotinamide can have undesirable effects. Excess nicotinamide inhibits sirtuins - the very enzymes that we actually want to activate with more NAD+【1】. Therefore, although nicotinamide is important for meeting vitamin requirements, it is suboptimal as an anti-ageing supplement if taken in high doses.
• Tryptophan: An essential amino acid that your body can also convert into niacin and ultimately NAD+. Tryptophan is found in poultry, cheese and soybeans, for example. In practice, however, this pathway is very inefficient - only a small fraction of the tryptophan ingested is converted to NAD+. The rest is used for other purposes (e.g. protein synthesis or serotonin formation).
• Nicotinamide riboside (NR): A relatively new star in the sky of NAD+ precursors. Chemically speaking, NR is a compound of nicotinamide and ribose (a sugar). It occurs naturally in traces in milk, for example【1】. NR was discovered in the 2000s as a third form of vitamin B3. It can be converted into NAD+ in the body in just one step - the enzyme pathway responsible is called NR kinase【3】. Nicotinamide riboside is now available as a dietary supplement (including the patented "Niagen"). You can find out more about why NR is receiving so much attention in a moment.
• Nicotinamide mononucleotide (NMN): Also a new NAD+ precursor, made popular by animal studies and advocates like Dr. Sinclair. NMN consists of nicotinamide plus a phosphate-ribose residue - so in a sense it is NR with a phosphate group. In the body, NMN is converted to NAD+ in two steps: first to nicotinamide (or NR), then to NAD+【4】. NMN occurs naturally in small amounts in broccoli or edamame, for example. Until recently, it was freely available as a supplement in the USA, but will probably be classified as a drug there and disappear from the market. In the EU, NMN is considered a novel food without authorization, which means that it cannot be sold freely. More on this in the section on the legal situation.

Bioavailability: How well do NR and NMN reach the cells?

An NAD+ supplement can only work if its active ingredient actually reaches your cells. This seemingly trivial statement has long been a point of contention between the advocates of NR and NMN. As mentioned, nicotinamide riboside (NR) has a slender structure - according to current knowledge, it can enter the bloodstream relatively easily from the intestine and be absorbed by the cells【3】. Interestingly, NR does not appear to need a detour for this: Cell membranes have special transporters that allow NR to enter directly【4】. NMN, on the other hand, is a larger molecule (it carries a phosphate group). Traditionally, biochemists assumed that NMN must first cleave off the phosphate group in order to enter the cell as NR【4】. However, recent research has identified a potential NMN-specific transporter in the intestine (called SLC12A8). So the debate is: does NMN have to convert to NR first, or can it do so directly? The answer seems to be: Both are possible. Some NMN is degraded to NR in the body (e.g. by the enzyme CD73 in the blood), but a certain proportion can be channeled directly into cells via SLC12A8【1】. In practice, this means that both NR and NMN can increase NAD+ levels - but they may do so with varying degrees of effectiveness in different tissues.

In fact, there is evidence from animal studies that NR achieves better results than NMN at certain sites in the body. In a comparative study on mice, the oral bioavailability of different precursors was tested. The result: NR significantly increased the NAD+ content in the liver and muscles, while there was no increase in the muscles when NMN was administered equimolar【4】. In other words: In this study, NR performed better than NMN, especially in terms of muscle. The activation of sirtuins (measured via a metabolic product called ADPR) was also most effective with NR - NR increased sirtuin activity many times more than nicotinamide【4】. In addition, in a mouse experiment, only NR (neither niacin nor NMN) prolonged the lifespan and stimulated damaged stem cells to regenerate【4】. These data indicate that NR is biologically very well utilized and reaches different organs. The high effectiveness of NR is attributed, among other things, to the fact that it has no phosphate group and can therefore pass through the cell membrane more easily【4】. NMN and NAD+ themselves, on the other hand, usually have to be broken down to NR before the cell can absorb them【4】.

However, there are also limitations: NR is highly bioavailable, but not super-stable. In the blood, some of the NR is broken down to nicotinamide within minutes (i.e. inactivated). This means that part of the orally ingested NR dose is "lost" on the way to the organs or only arrives as nicotinamide. Researchers are already working on improvements - for example on NRH, a reduced form of nicotinamide riboside, which should be more stable and could increase NAD+ even faster. However, such developments are still experimental. For the time being, nicotinamide riboside remains the best available and researched precursor.

Legal situation: Can NMN be taken at all?

An important practical point before we delve deeper into the studies: In the EU, nicotinamide mononucleotide (NMN) is currently not authorized as a food supplement. The European Food Safety Authority (EFSA) considers NMN to be anovel ingredient(novel food) for which there is a lack of sufficient safety testing. In November 2022, the EU Commission clarified that NMN is not marketable until further notice. Reputable manufacturers therefore do not offer NMN in Europe. NMN was freely available in the USA until recently, but the FDA is also pulling the emergency brake: as NMN is under review there as a possible drug substance, it could soon disappear from the supplement shelves in the States too. Nicotinamide riboside (NR), on the other hand, is approved in the EU (NR chloride was approved as a novel food in 2020) and is considered safe in the recommended dosages. It is subject to strict quality controls and can be legally sold as a food supplement. For you as a consumer, this means staying away from dubious NMN powders of unknown origin that may be offered online and instead opting for NR products from established manufacturers. This will keep you within a safe and legal framework. (If you still want to experiment - for example via private import from countries such as Japan, where NMN is freely available for sale - bear in mind that the scientific data on long-term effects is limited and consult a doctor if in doubt).

Nicotinamide riboside: The favorite among the NAD+ precursors

Now we come to the real star of this topic: nicotinamide riboside (NR). Why are so many scientists and biohackers raving about it? We have already learned a lot about its good bioavailability. But at least as important is the scientific evidence that has accumulated on NR in recent years. Let's take a look at the most important findings and studies - in humans and in preclinical models:

• Safe and well tolerated: several clinical studies have confirmed the safety of nicotinamide riboside. As early as 2016/2017, an initial pilot study showed that NR is efficiently absorbed by the human body and increases NAD+ levels in the blood in a dose-dependent manner - without serious side effects【5】. In an open trial, the NAD+ level of healthy volunteers increased up to 2.7-fold after NR administration【5】. Later placebo-controlled studies underpinned the safety: doses of up to 1000 mg/day were well tolerated, and even 2000 mg/day over several weeks did not cause any dangerous effects【1】. Important: Unlike high doses of niacin, NR does not cause a flush because it does not activate the GPR109A receptor【1】. The US FDA has even classified NR as "generally safe"(GRAS)【1】. For users, this means that standard doses (usually 250-300 mg per day, often split between morning and evening) are considered safe. Of course, every body reacts individually - but no serious side effects have been documented to date.
• Increase in cell energy and metabolic health: As NR replenishes the NAD+ balance, it stands to reason that this has a positive effect on cell metabolism. Animal studies provided impressive results early on: Mice with high levels of NR in their diet gained less weight, had better glucose metabolism and a lower tendency to develop fatty liver - even when fed a high-fat diet【1】. (The relationship between nicotinamide riboside and metabolic health has not yet been confirmed by EFSA; further studies are required). In a mouse model of type 2 diabetes, NR also improved insulin sensitivity and reduced fatty liver formation【1】. What about in humans? One of the first human studies (2018, published in Nature Communications) investigated NR in middle-aged and older adults. The participants received 250 mg NR twice a day for 6 weeks. The result: the NAD+ level in the blood cells increased significantly and - excitingly - in people with slightly elevated blood pressure, the systolic value decreased by an average of 8 mmHg【7】. Aortic stiffness (a marker of vascular health) also improved【7】. These findings suggest that NR may have a beneficial effect on age-related changes in the cardiovascular system【7】. (The relationship between nicotinamide riboside and age-related cardiovascular risk factors has not yet been confirmed by EFSA; further studies are required). However, another study on obese men found no improvement in insulin action - despite significantly increased NAD+ levels【1】. The authors suspect that 12 weeks may have been too short or that obese participants require stronger interventions. Conclusion so far: NR can improve measurable metabolic parameters in humans (especially in the cardiovascular area), but it is not a miracle cure that will single-handedly make diabetes & co. disappear. Further research is ongoing, including on NR in combination with exercise and diet.
• Mitochondria & muscle strength in old age: Muscle function in the elderly is an exciting field of application. Mitochondria in our muscle cells lose performance with age - we become less powerful and tire more quickly. As NAD+ is central to mitochondrial energy production, it seemed obvious that NR could be used here. In 2019, a team of researchers tested acute NR supplementation in older people (average age ~75 years) in a cross-over design. Even a single dose of NR (1000 mg) significantly improved certain performance parameters during endurance training in this study【9】. Signs of an improved redox balance were also found, meaning that cells were better able to absorb oxidative stress【9】. These results give us hope that NR could help to maintain physical fitness in old age. (The relationship between nicotinamide riboside and the maintenance of physical fitness in old age has not yet been confirmed by EFSA; further studies are required). However, these were short-term effects; future studies must show whether long-term NR intake slows down muscle atrophy(sarcopenia).
• Cell protection in diseases: Away from the issue of longevity, NR is also being researched for possible therapeutic effects. Some examples: In a mouse study, NR stimulated the regeneration of the hematopoietic system after high-dose radiation - the animals recovered faster from radiation damage to the bone marrow【6】. This suggests that NR could be useful as a support during chemotherapy or radiotherapy. Another study found that NR administration in rats alleviated the peripheral neuropathy caused by a chemotherapeutic agent (paclitaxel)【8】. The animals suffered less pain and nerve damage when they received NR in parallel. Such results are of course preliminary and from animal models - but they show the broad spectrum of possible effects NAD+ precursors can have. From neurodegenerative diseases to liver health and immune function (there are indications that NR supports the defense against certain viral infections in mouse models), many things are being investigated. Much of this research is still in its infancy. Nevertheless, the many positive preclinical findings underpin the status of nicotinamide riboside as a multi-talented vital substance. (Of course, these correlations have not yet been confirmed by the EFSA; further studies are required).

Admittedly, NR sounds almost too good to be true. Therefore, for the sake of completeness: not all studies were brilliant. There have also been disappointments - such as the aforementioned attempt to improve insulin resistance in severely overweight people, which was unsuccessful. It is also still unclear what the long-term effects of NR will be: Do NAD+ levels stay up permanently? Are there perhaps effects after years that are not seen in short-term studies? Such questions are still open. However, animal studies at least do not indicate any serious long-term problems - on the contrary, mice lived longer and remained healthier. Nevertheless, the scientific community believes that further studies, especially large controlled studies on humans, are needed to draw definitive conclusions. Until then, we remain in a gray area between promising evidence and cautious optimism.

NMN: The challenger - and why nicotinamide riboside has the edge

Having looked at nicotinamide riboside in detail, we don't want to ignore nicotinamide mononucleotide (NMN) - after all, NMN is the direct predecessor of NR, so to speak. How does NMN compare? Very similar in some respects: NMN also increases NAD+ levels in many animal models, improves metabolic functions and has shown impressive effects in mouse experiments. A study from 2013, for example, which contributed significantly to the fame of NMN, showed that old mice developed a better sugar metabolism and more stamina through NMN administration - as if they were metabolically young again【2】. In a recent study on overweight women with prediabetes (published in Science in 2021), NMN was tested in humans for the first time: Over 10 weeks, the participants were given 250 mg NMN or placebo daily. The result: NMN significantly increased the insulin sensitivity of the muscles and improved gene activity in muscle cells towards better structure and sugar uptake【10】 - an indication that NMN can have a positive influence on muscle metabolism in older people. (The links between NMN and insulin sensitivity and muscle metabolism have not yet been confirmed by the EFSA; further studies are required). It should be noted that this was about a special group (postmenopausal women with impaired sugar metabolism). For healthy people, the data on NMN is still very thin. Nevertheless, there is a small Japanese study that proved the acute safety of NMN: ten men received single doses of up to 500 mg, and no serious side effects or changes in laboratory values occurred【11】. NAD+ levels also increased significantly with NMN, and some blood values (e.g. triglycerides) tended towards improvement【11】. (The correlations between NMN and metabolic parameters have not yet been confirmed by the EFSA; further studies are required). So there are certainly comparisons with NR - NMN also works in principle.

So why do many experts still favor nicotinamide riboside? It can be broken down into three key points:

1. Study situation: There is significantly more clinical data available on NR. More than ten published human studies (including several placebo-controlled studies) have looked at the efficacy and safety of NR【1】. NMN is only at the beginning here - most of the results come from animal experiments. As far as long-term safety is concerned, for example, we already know that NR is safe even when taken in high doses for several weeks【1】. Such a comprehensive characterization is still lacking for NMN. This knowledge gap makes us cautious. At the same time, with NR we have the advantage that "unproductive" studies (such as those on obese men) have already been carried out - we know where NR alone may not be sufficient. NMN could also reach its limits in similar scenarios; we just haven't studied it yet. To summarize: NR is better supported by science, which builds confidence.
2. Legal and qualitative aspects: As explained above, NMN is not legally available as a dietary supplement in Europe (and possibly soon in the US). Consumers who nevertheless obtain NMN often resort to questionable online sources. The risk of contamination or incorrect dosage is considerable. NR, on the other hand, is available from reputable manufacturers in tested quality (often in pharmacies or directly from the manufacturer). In addition, NR is officially recognized as a source of vitamin B3, while NMN is pending regulatory approval. NR therefore enjoys an advantage in terms of trust, simply because it has the official blessing and is produced transparently.
3. Efficiency and effects: Although direct comparative studies on humans have yet to be carried out, the available data tends to speak in favor of NR. The findings from animal experiments mentioned above - NR increases NAD+ in muscle and liver more than NMN at the same dose【4】 - indicate that NR is at least as effective, if not more so in some tissues. NR also appears to boost more downstream activities(sirtuin function, stem cell protection)【4】. And in purely practical terms: many users report anecdotally that they feel more energetic and regenerate better with NR - experiences with NMN are rare due to a lack of distribution. Of course, personal reports are not hard evidence, but they underpin the trend. As long as NMN is not clearly superior somewhere, there are few arguments to disgrace the tried and tested NR.

Interim conclusion: Nicotinamide riboside is currently ahead when it comes to raising NAD+ levels. This does not mean that NMN is ineffective or "bad" - both substances are probably useful. But for the reasons mentioned, NR is currently the gold standard among NAD+ precursors. So if you want to do something for your NAD+ levels today, you can't go wrong with nicotinamide riboside. NMN remains an exciting subject of research and could play a supplementary role in the future - if approvals are granted. But for now: go for the approved and researched option.

Tips for everyday life: How you can support your NAD+ levels

• Exercise and regular sport: Physical activity increases the activity of enzymes such as NAMPT, which are involved in NAD+ recycling (salvage pathway). Studies show that endurance training in muscles promotes NAD+ production and at the same time reduces the harmful effects of ageing (e.g. inflammation). Your motto: "Use it or lose it." Just 3-4 units of moderate exercise per week can help to counteract age-related NAD+ consumption in the long term.
• Sleep and circadian rhythm: Perhaps surprisingly, your sleep-wake rhythm influences your NAD+ metabolism. NAD+ and the internal clock of the cells are linked - poor sleeping habits can disrupt this rhythm. Make sure you get enough sleep and maintain a regular rhythm. Pulling an all-nighter may make you feel young, but it means stress and NAD+ loss for your cells.
• Eat a healthy diet with sources of vitamin B3: Make sure your basic supply of niacin is right. Good sources include poultry, tuna, salmon, peanuts, green vegetables and whole grains. As a rule, niacin deficiency is rare nowadays - but if you eat a one-sided diet, you could be taking in too little. Also consider other nutrients that promote NAD+: B vitamins as a whole (B2 and B6 help with NAD+ synthesis), polyphenols such as resveratrol (activate sirtuins indirectly) and antioxidants (they reduce NAD+ consumption through oxidative damage). A colorful, wholesome diet supports your metabolism on all levels.
• Calorie restriction / intermittent fasting: Studies on animals have shown that intermittent fasting or moderate long-term calorie restriction can increase the NAD+ concentration. The reason: fasting results in less NAD+ consumption through digestion and less formation of NAD+ predators (such as pro-inflammatory signaling substances). In addition, the production of ketone bodies increases, which can serve as a signal for the sirtuins. Of course, strict fasting is not suitable for everyone - but approaches such as 16/8 intermittent fasting (16 hours fasting, 8 hours eating window) can often be easily integrated into everyday life. They could help to keep your NAD+ levels higher in the long term.
• Food supplements with brains: If you decide to use an NAD+ precursor as a dietary supplement, choose the product carefully. Pay attention to purity, manufacturer's instructions and dosage recommendations. In Germany and the EU, you can legally use nicotinamide riboside. For example, XTRAFUEL offers its own nicotinamide riboside complex, which relies on pharmacy quality and combines synergistic vital substances. Such products provide a defined amount of NR per capsule - often in the 100-300 mg range - and are formulated to be easy to take on a daily basis. Stick to the recommended daily intake, because "a lot helps a lot" does not apply: your body cannot utilize excess NR indefinitely and excretes it. Also consider whether you take NR permanently or in cycles (e.g. 8-week course, then break). Experience reports vary here and there are no scientific guidelines yet. Listen to your body feeling and talk to a doctor if in doubt, especially if you are taking medication or have pre-existing conditions.

Conclusion: Staying young longer with NAD+ - a realistic goal?

Research into NAD+ and longevity is still in its infancy, but the findings to date are cautiously optimistic. NAD+ is a key molecule in cellular health, and maintaining or increasing it could be a key to mitigating ageing processes - at least at the cellular level. (The links between NAD+ balance and ageing processes are not currently confirmed by EFSA; further studies required). Nicotinamide riboside (NR) has established itself as a practical and safe way to replenish NAD+ reserves. It scores with good bioavailability, a growing number of positive studies and legal availability in high quality. NMN remains an exciting candidate, but currently it has to watch from the sidelines as it is not (yet) widely approved and less data is available. What this means for you: If you want to do something good for your cells and possibly invest in healthy ageing, you can try nicotinamide riboside. Don't expect miracles overnight - ageing is a complex process that cannot be "switched off" with a single molecule. But science provides evidence that by increasing your NAD+ levels, you could give your cellular health a head start. Combined with a conscious lifestyle, this is a promising approach to getting fit and energized as you age.

The next few years will certainly bring even more insights. Until then: stay curious, get information from reputable sources and listen to your body. Because the best investment in longevity is still an informed, holistic approach - with the right amount of science behind it. With this in mind: here's to a healthy, long life full of energy! 🏃♂️🥦

Frequently asked questions about NAD+ precursors (FAQ)

• Can't you just take NAD+ directly instead of precursors?
  Direct NAD+ as a supplement is problematic because the molecule passes very poorly through cell membranes and is quickly broken down in the body. NAD+ would be broken down into its components in the digestive tract and would hardly enter the bloodstream. This is why precursors (such as NR or NMN) are used, which the body can easily absorb and then convert into NAD+. Although there are experimental approaches with NAD+ infusions (i.e. NAD+ directly into the blood), these are expensive, potentially risky and have not yet been sufficiently scientifically investigated. For most purposes, NAD+ precursors in capsule form are the more practical and safer option.
• What time of day should I take NAD+ precursors?
  There are no official guidelines on this yet. Many users take nicotinamide riboside in the morning, sometimes on an empty stomach, to increase NAD+ levels early in the day. Others split the dose and take one capsule in the morning and one in the evening to keep NAD+ levels more constant. As NR can have a stimulating effect (increased metabolism), some people refrain from taking it late at night so as not to disturb their sleep. Basically, try out what works for you. The important thing is to take it regularly rather than at exactly the right time.
• Is an NAD+ supplement suitable for everyone?
  Nicotinamide riboside is considered very safe at recommended doses and is generally well tolerated. Nevertheless, certain groups of people should be cautious: pregnant or breastfeeding women as well as children and adolescents should only take NAD+ precursors after consulting a doctor, as there are hardly any studies available. Even if you suffer from a serious illness or regularly take medication (e.g. blood thinners, cancer medication), discuss the intake with your doctor beforehand. Otherwise, NAD+ precursors are considered safe for healthy adults - however, they do not replace a healthy lifestyle, but rather supplement it.
• How quickly do you notice the effect?
  This varies from person to person. Some users report a slight increase in energy and shorter recovery times after exercise after just a few weeks. Studies have often shown certain improvements (e.g. in blood pressure or muscle metabolism) after 6-8 weeks. However, dramatic rejuvenation effects are not to be expected - the benefits are subtle and rather long-term. It is important to take it consistently over a longer period of time. If you do not notice any effect after 2-3 months, you can reconsider your strategy. Many factors (diet, sleep, genes) influence the effect, so experiences vary.
• Is nicotinamide riboside the same as niacin or niacinamide?
  No, even though all three substances are forms of vitamin B3, there are differences: Niacin (nicotinic acid) and niacinamide (nicotinamide) are the classic forms of vitamin B3 and are used in many multivitamin supplements. Nicotinamide riboside (NR) is a newer, special form of vitamin B3 that also has a ribose sugar molecule bound to it. This allows NR to utilize different metabolic pathways in the body than niacin or niacinamide. Above all, NR increases the NAD+ level very efficiently without triggering the typical side effects of niacin (flushing). Niacin and niacinamide are excellent for preventing vitamin B3 deficiency, but NR (and NMN) are considered more effective when it comes to specifically increasing the NAD+ balance.
• Can a healthy diet replace the intake of NAD+ precursors?
  A balanced diet with sufficient vitamin B3 (niacin) and protein-rich foods (for tryptophan) is the basis for a normal NAD+ balance. A healthy lifestyle - with lots of vegetables, fruit, exercise and little chronic stress - helps your body to maintain NAD+ levels. NAD+ precursors are the "icing on the cake", so to speak, to give you an extra boost in old age or under particular stress. They cannot make up for an unhealthy lifestyle, but they can - on the basis of a good lifestyle - provide an additional benefit. If you are young, in good health and eating optimally, you may feel little difference. However, as you age or if you have certain health challenges, NAD+ precursors may be a worthwhile supplement.

Sources

1. [1] Verdin, E. et al (2020). Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients, 12(6), 1616. DOI: 10.3390/nu12061616 (review article with comprehensive information on NAD+, sirtuins and nicotinamide riboside).
2. [2] Gomes, A.P. et al (2013). Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell, 155(7), 1624-1638. DOI: 10.1016/j.cell.2013.11.037.
3. [3] Trammell, S.A. et al. (2016). Nicotinamide riboside is uniquely and orally bioavailable in mice and humans. Nature Communications, 7, 12948. DOI: 10.1038/ncomms12948.
4. [4] Rajman, L. et al (2018). NAD+ as an integrator of metabolism and signaling in aging and disease. Science, 350(6265), 1208-1213. DOI: 10.1126/science.aac4854 (Review article on NAD+ metabolism; contains data on NR vs. NMN in mice).
5. [5] Airhart, S.E. et al. (2017). An open-label, non-randomized study of the pharmacokinetics of nicotinamide riboside and its effects on blood NAD+ levels in healthy volunteers. PLoS ONE, 12(12), e0186459. DOI: 10.1371/journal.pone.0186459.
6. [6] Vannini, N. et al (2019). The NAD-booster Nicotinamide Riboside potently stimulates hematopoiesis through increased mitochondrial clearance. Cell Stem Cell, 24(3), 405-418.e7. DOI: 10.1016/j.stem.2019.02.012.
7. [7] Martens, C.R. et al (2018). Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nature Communications, 9, 1286. DOI: 10.1038/s41467-018-03421-7.
8. [8] Hamity, M.V. et al (2017). Nicotinamide riboside relieves paclitaxel-induced peripheral neuropathy in female rats. Pain, 158(6), 962-972. DOI: 10.1097/j.pain.0000000000000862.
9. [9] Dolopikou, C.F. et al (2020). Acute nicotinamide riboside supplementation improves redox homeostasis and exercise performance in old individuals: a double-blind cross-over study. European Journal of Nutrition, 59(2), 505-515. DOI: 10.1007/s00394-019-01919-4.
10. [10] Yoshino, M. et al (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science, 372(6547), 1224-1229. DOI: 10.1126/science.abe9985.
11. [11] Irie, J. et al (2020). Effect of oral administration of nicotinamide mononucleotide on clinical parameters and nicotinamide metabolite levels in healthy Japanese men. Endocrine Journal, 67(2), 153-160. DOI: 10.1507/endocrj.EJ19-0313.