Nicotinamide riboside (NR) is a chemical compound that acts as a NAD+ precursor and can be converted into NAD+ in our body. NAD+ is a significant cofactor for many important biochemical reactions. Additionally, NR belongs to the class of B3 vitamins and plays a crucial role in the electron transport chain in the mitochondria, the "powerhouses" of our cells. Therefore, it is critically involved in the energy supply of our body.
We will take a closer look at the research on nicotinamide riboside (NR) and explain the role of the molecule in aging research and in our body. Don't worry, even though there are many scientific abbreviations in some places, we will break down the complex relationships as clearly as possible.
What is Nicotinamide Riboside (NR)?
Nicotinamide Riboside is often used as a dietary supplement as it may potentially improve energy production, cognitive performance and cellular regeneration. Although the long-term effects of NR are not yet fully understood, there are numerous studies suggesting that it could be a promising approach to healthy aging .
Recent research indicates that taking Nicotinamide Riboside may help counteract age-related diseases and improve cellular respiration, making it a promising agent in terms of health maintenance and prevention.
NR, NAD, NAM, Niacin, … a brief profile of the molecules
You may have already noticed in the first lines that besides Nicotinamide Riboside (NR), several other molecules play a role. If you want a detailed insight into the science, you can read our NAD article. To help you keep track throughout this post, we will briefly explain the most important players in NAD metabolism. This way, you can better understand the similarities and differences later:
- NAD (Nicotinamide Adenine Dinucleotide): NAD is an essential coenzyme found in all living cells. It plays a central role in energy metabolism, particularly in cellular respiration, by transporting electrons between molecules. NAD exists in two forms: NAD+ (oxidized form) and NADH (reduced form).It is important for the production of ATP, the energy unit of the cell, and is involved in various other biochemical processes such as DNA repair and gene expression
- NR (Nicotinamide Riboside): NR is a form of Vitamin B3 (Niacin) and a precursor to NAD. It can be taken orally (as a tablet or powder) and is converted to NAD in the body. NR is used as a dietary supplement to increase NAD levels.
- NAM (Nicotinamide): NAM, also known as Niacinamide, is another form of Vitamin B3. It is a precursor to NAD and can be converted to NAD in the body. However, the metabolic pathway is different from that of NR.NAM also has independent medical applications and is often used in skincare products as it has anti-inflammatory properties and can strengthen the skin barrier.
- Niacin: Niacin, also known as Vitamin B3 or nicotinic acid, is an essential vitamin that is converted in the body to NAD and NADP+. It is important for energy metabolism and the synthesis of fatty acids and cholesterol. Niacin is also used to treat dyslipidemia as it can help lower cholesterol levels.
By the way: There are many different spellings for NAD (Nicotinamide Adenine Dinucleotide) : NAD, NADH, NAD+, to name just a few. To simplify things a bit, we will stick with NAD.
Where does Nicotinamide Riboside occur?
Nicotinamide Riboside is a molecule that can occur in small concentrations in some foods.This includes dairy products and yeast. However, studies show that the NR concentrations in foods tend to be low.
Since 2013, it has been possible to chemically produce Nicotinamide Riboside in a complex manner, leading to extensive research in studies as well as its use as a dietary supplement .
Although it may be difficult to obtain NR through diet alone, its use as a supplement is popular due to its potential health benefits.
Nicotinamide riboside occurs naturally in the following foods
- Cow's milk
- Various types of yeast
- Various types of beer
Although these foods contain small amounts of nicotinamide riboside, the most effective method to ensure an adequate intake is through supplementation. The amount of NR in milk is only 4.8 micromoles per liter, which is significantly below the therapeutically required amount.
What function does nicotinamide riboside have in the human body?
Nicotinamide riboside plays an important role in the human body. It is a precursor of the coenzyme NAD+, which is involved in numerous biochemical reactions that are essential for energy production, the cell cycle, and DNA repair.
Research has shown that NR also has a antioxidant effect and can optimize the cellular metabolism . It is suspected that an adequate supply of NR could have positive effects on the cardiovascular system and may also slow down aging processes.
What are the benefits of supplementing with Nicotinamide Riboside?
Supplementing with Nicotinamide Riboside offers numerous benefits.
On one hand, there is a correlation between the decreasing NAD+ levels in age-related diseases. NR has been able to increase this level again in scientific studies.
On the other hand NR has a beneficial effect on the body's own synthesis of ATP, as many enzymes (including the Sirtuins) require NAD+ for their function. Thus, supplementation with NR helps protect us from oxidative stress, inflammation or DNA damage .
These enzymes play an important role in repairing our genetic material and the physiological stress response. It is believed that a decrease in NAD+ can impair the function of the Sirtuins and may promote age-associated diseases.
Studies have shown that supplementation with NR can improve or increase the concentration of NAD+ in cells, insulin sensitivity, mitochondrial function, the function of stem cells , and the activity of sirtuins. Additionally, Nicotinamide Riboside has significantly fewer potential side effects compared to other NAD+ precursors .
These are the differences between Nicotinamide Riboside, Vitamin B3, and NAD+
Nicotinamide Riboside, Nicotinamide adenine dinucleotide (NAD+), and Vitamin B3 are all involved in the energy metabolism of the organism.
NAD+ is a coenzyme that is important for the functionality of various enzymes involved in cellular energy production.
Vitamin B3, also known as niacin, is a water-soluble vitamin that plays a crucial role in converting food into energy. NR is a specific form of vitamin B3.
Nicotinamide riboside is a relatively new discovery and is used as a dietary supplement. There are some differences between these substances. NAD+ is a naturally occurring coenzyme in the body that is involved in several biological processes, while vitamin B3 (niacin) is an essential nutrient primarily obtained through food but also exists naturally in the body.
Differences between Nicotinamide Riboside (NR) and Nicotinamide (NAM)
Nicotinamide Riboside and Nicotinamide (NAM) are both variants of vitamin B3.
The central difference between Nicotinamide Riboside and NAM lies in their chemical composition and their metabolic processing in the body.
NR is a form of niacin that is converted in the body into nicotinamide adenine dinucleotide (NAD+). NR is considered a precursor of NAD+ as it can be transformed into NAD+ through a sequence of enzymatic reactions.
Compared to NAM, NR is generally considered a more effective precursor for NAD+ as it is less dependent on other metabolic processes for NAD+ formation. In the administration of NAM, there were z.B in some preclinical studies, painful "flushing" episodes.
Did you know?
Niacin was one of the first medications used against high blood lipid levels (hypercholesterolemia). Niacin was able to lower LDL levels but had a significant drawback. At high doses, it could cause the so-called "flush," where people turned red. For this reason, niacin has never fully established itself as a medication against high blood lipid levels.
NR vs.other NAD boosters
Admittedly, the difference between the various precursor molecules of NAD and their individual advantages and disadvantages is even more complicated than the similar naming.
But what makes Nicotinamide Riboside (NR) special? What sets it apart from other NAD precursors?
On one hand, there is the extensive study background. No other molecule has such a comprehensive body of research involving humans. On the other hand, the bioavailability and proven increase in NAD, not only in the blood but also in the muscle, speaks for NR. The reason NR particularly reaches the muscle and heart is likely due to physiology. One of the pathways through which NR enters (muscle) cells is via a transporter with the cryptic abbreviation Nmrk 2. This is found particularly often in heart and skeletal muscle cells, but also in liver cells.
Did you know?
Studies on the transporter Nmrk2 are still quite rare, but it could potentially play a role in the therapy of heart failure in the future. This condition encompasses a whole range of pathomechanisms, ultimately leading to reduced heart performance. One possible reason could be that Nmrk2 is downregulated in cardiac muscle cells, resulting in a poorer NAD metabolism, which ultimately leads to mitochondrial dysfunction.
Nicotinamide Riboside Dosage – these are the recommendations
The Federal Institute for Risk Assessment (BfR) specifies a maximum amount of 160 mg per daily intake recommendation for nicotinamide. However, depending on the study, the dosage varies significantly, with between 300mg and 2000mg used daily in the studies.A clear statement regarding the dosage of Nicotinamide Riboside cannot be made accurately so far.
What are the benefits of supplementing with Nicotinamide Riboside?
Supplementing with Nicotinamide Riboside offers numerous benefits. On one hand, there is a correlation between the decreasing NAD+ levels and age-related diseases. NR has been shown in scientific studies to increase this level again. On the other hand, NR positively affects the body's own synthesis of ATP, as many enzymes require NAD+ for their function.
Did you know?
Nicotinamide Riboside affects the composition of the microbiome according to this study.Here, twins were treated with NR for 5 months, and alongside an improved NAD metabolism, there was also an improvement in the composition of the gut flora. To be precise, NR increased the presence of Faecalibacterium prausnitzii. This bacterium is associated with better metabolic health and seems to have anti-inflammatory effects.
Nicotinamide Riboside and Parkinson's – initial results
Scientists have long suspected that in some neurological diseases, the metabolism of nerve cells plays a role. Decreasing NAD levels could negatively affect the mitochondria (the power plants of the cells) and thus influence the performance of our nerve cells. At least, this is the hypothesis.One of these neurological diseases, in which nerve cells in the brain deteriorate, is Parkinson's. Here dopaminergic neurons in the brain gradually die off, leading to the typical symptoms.
To test their hypothesis, the scientists examined 30 patients in the NADPARK study according to the highest scientific standards (i.e., double-blind, randomized).
Half of the participants received 1000mg Nicotinamide Riboside per day for 30 days. In the end, the scientists were able to demonstrate that NR could increase NAD levels in the brain. But not only that, the participants with Nicotinamide Riboside even showed an improvement in their cognitive performance.
Although this was only a small study, it clearly shows that even high doses of NR are well tolerated and that a measurable success occurs.It certainly won't be the last study on Nicotinamide Riboside and Parkinson.
Liposomal NR, Nicotinamide Riboside Chloride – what forms are there?
Liposomal NR is a form of Nicotinamide Riboside that is encapsulated in liposomes. Liposomes are tiny fat bubbles that help transport active ingredients directly into the cells and increase bioavailability. However, the study situation here is still not very good. The higher bioavailability is more of a hypothesis than a confirmed fact. You can find more about the different ways to increase bioavailability in our article on absorption pathways.
Nicotinamide Riboside alone would not last long and would not be well absorbed by our intestines. For this reason, it is often combined with chloride to obtain Nicotinamide Riboside Chloride.This form of NR is significantly more stable and can thus increase bioavailability.
High homocysteine levels due to NAD precursors?
Supplementation with NR can increase NAD levels. At the same time, researchers found in some studies that homocysteine levels also increased.
Homocysteine is an amino acid whose increased occurrence is considered a confirmed risk factor for the development of cardiovascular diseases. How does this fit together? On one hand, NR seems to have positive effects on the heart, as shown in this study where Nicotinamide Riboside increased NAD levels within the heart and thus indirectly contributed to improved mitochondrial function in the heart. On the other hand, NR seems to increase a risk factor for the development of arteriosclerosis with homocysteine.The explanation lies in the metabolism of the molecule.
Methyl groups as a crucial factor
To better understand the homocysteine issue, we need to take a close look at the NAD metabolism. Simply put, there are different pathways in NAD metabolism through which we can regenerate NAD from precursor molecules, such as NR or NAM. These conversions require so-called methyl groups. These are compounds made up of carbon and hydrogen atoms that are easily transferable. If we now increase the intake of precursors, in our case Nicotinamide Riboside, then there is an increased conversion of these precursors into NAD. Our desired effect, higher NAD levels, is thus achieved.
However, the body also needs some methyl groups for this. And this is where homocysteine comes into play.On one hand, homocysteine is an intermediate product in this metabolism, and on the other hand, our body needs methyl groups to convert homocysteine into a harmless form. This explains the researchers' findings.
Once again, summarized as simply as possible. The hypothesis is: The conversion of NR to NAD requires methyl groups. The consumption of methyl groups leads to higher homocysteine levels.
Did you know?
Methyl groups are involved in numerous processes in our body. They are also involved in the regulation of our DNA. With the help of methyl groups, our body can control which part of the DNA is read and which is not. Similar to volume controls, certain areas become louder (active) or quieter (inactive). The field of research for this is called epigenetics.
Betaine-TMG – a safe supplement
We have already seen that the intake of NAD precursors can potentially lead to higher homocysteine levels. It should be noted that this does not necessarily have to be the case. In the studies, this could not always be demonstrated, and there seems to be a personal predisposition for it.
A possible solution to this problem is to provide the body with more methyl groups. Therefore, we need a methyl group donor, and this is exactly what the molecule betaine can do. There are different forms available. Betaine-TMG is the crucial one, as it can lower homocysteine levels as a methyl group donor, while betaine-HCL supports the production of stomach acid. Similar name, but completely different application.
Conclusion on Nicotinamide Riboside
NR is a promising Longevity-molecule. Studies have shown that it increases the concentration of NAD+ in cells, thereby having positive effects on insulin sensitivity, mitochondrial function, stem cell activity, and the function of sirtuins. What makes Nicotinamide Riboside particularly interesting is its status as “GRAS” (generally regarded as safe) – it is therefore generally considered safe. These promising results raise hopes for a longer and healthier lifespan.
