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Nicotinamide Riboside (NR)

Nicotinamide Riboside (NR)

Nicotinamide riboside (NR) is a chemical compound that acts as an NAD+ precursor and can be converted into NAD+ in our body. NAD+ is an important cofactor for many important biochemical reactions. NR also belongs to the class of B3 vitamins and plays a crucial role in the respiratory chain in the mitochondria, the "power plants" of our cells. Thus, it plays a crucial role in supplying our body with energy.

We take a closer look at the studies on nicotinamide riboside (NR) and explain the role the molecule plays in ageing research and in our bodies. Don't worry, even if there are a lot of 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 because it can 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 may represent a promising approach to healthy ageing .

Recent research suggests 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 will no doubt have noticed in the first few lines that, in addition to the nicotinamide riboside (NR), several other molecules also play a role. If you want a more detailed insight into the science, you can read our NAD article. So that you don't lose track of things in the course of this article, we will briefly explain the most important players in NAD metabolism. This will help you to better understand the similarities and differences later on:

  • NAD (nicotinamide adenine dinucleotide): NAD is an essential coenzyme that is 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 of NAD. It can be taken orally (as a tablet or powder) and is converted into 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 of NAD and can be converted into NAD in the body. However, the metabolic pathway is different to that of NR. NAM also has medicinal applications in its own right 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 into NAD and NADP+ in the body. 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: NAD (nicotinamide adenine dinucleotide) has many different spellings: NAD, NADH, NAD+ to name just a few. To simplify things a little, we'll stick with NAD.

Where does nicotinamide riboside occur?

Nicotinamide riboside is a molecule that can be found in low concentrations in some foods. These include dairy products and yeast. However, studies show that the NR concentrations in food tend to be low.

Since 2013, it has been possible to produce nicotinamide riboside chemically at great expense, which has led to extensive research in studies and to 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

  • Milk from cows
  • Various types of yeast
  • Various types of beer

Although these foods contain small amounts of nicotinamide riboside, the most effective way to ensure adequate intake is to take supplements. The amount of NR in milk is only 4.8 micromoles per liter, which is well below the therapeutic requirement.

What is the function of nicotinamide riboside 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 reactionsthat are essential for energy production, the cell cycle and DNA repair.

Research has shown that NR also has an antioxidant effect and can optimize cell metabolism . It is assumed that a sufficient supply of NR could have positive effects on the cardiovascular system and possibly also slow down ageing processes.

What are the benefits of supplementing with nicotinamide riboside?

Supplementing with nicotinamide riboside offers numerous benefits.

Firstly, there is a correlation between decreasing NAD+ levels and age-related diseases. NR was 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 sirtuins) require NAD+ to function. Supplementing with NR therefore helps to protect us from oxidative stress, inflammation or DNA damage .

These enzymes play an important role in the repair of our genetic material and the physiological stress response. It is assumed that a decrease in NAD+ impairs the function of sirtuins and can promote age-associated diseases .

Studies have shown that supplementation with NR increases the concentration of NAD+ in the cells, the insulin sensitivitythe mitochondrial function, the function of stem cells and the activity of sirtuins can be improved or increased. Nicotinamide riboside also has significantly fewer potential side effects compared to other NAD+ precursors .

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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 organism's energy metabolism.

NAD+ is a coenzyme that is important for the functionality of various enzymes involved in cell energy production.

Vitamin B3, also known as niacin, is a water-soluble vitamin that plays a crucial role in the conversion of food to energy. NR is a specific form of vitamin B3.

Nicotinamide riboside is a fairly recent 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 that is mainly ingested through food, but also exists naturally in the body.

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Differences between nicotinamide riboside (NR) and nicotinamide (NAM)

Nicotinamide riboside and nicotinamide (NAM) are both variants of the B3 vitamin.

The key 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 into nicotinamide adenine dinucleotide (NAD+) in the body. 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 to be a more effective precursor for NAD+ as it is less dependent on other metabolic processes for NAD+ formation. The administration of NAM z.Bin some preclinical studies resulted in painful "flushing" seizures.

Wusstest Du?

Niacin was one of the first drugs used to treat high blood lipid levels (hypercholesterolemia). Niacin was able to lower the LDL level, but had a decisive disadvantage. High doses could lead to a so-called "flush", which caused people to turn red. This is another reason why niacin has never fully established itself as a drug 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?

Firstly, there is the long study length . No other molecule has been studied so extensively in humans. Secondly, the bioavailability and demonstrable increase in NAD,not only in the blood but also in the muscle, speaks in favor of NR. Why NR reaches the muscle and heart in particular is probably due to physiology. E One of the routes by which NR enters the (muscle) cells is via a transporter with the cryptic abbreviation Nmrk 2. This is found particularly often on heart and skeletal muscle cells, but also on liver cells.

Wusstest Du?

Studies on the transporter Nmrk2 are still quite scarce, but the transporter could possibly play a role in the therapy of heart failure in the future. This clinical picture comprises a whole range of pathomechanisms, at the end of which there is a reduced performance of the heart. One possible reason could be that Nmrk2 is downregulated in the heart muscle cells, resulting in 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, the dosage varies greatly depending on the study. Between 300mg and 2000mg per day are used in the studies. A clear statement on the nicotinamide riboside dosage can therefore not yet be made exactly.

What are the benefits of supplementing with nicotinamide riboside?

Supplementing with nicotinamide riboside offers numerous benefits. Firstly, there is a correlation between the falling NAD+ level in age-related diseases. NR was 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 require NAD+ to function.

Wusstest Du?

Nicotinamide riboside has an effect on thecomposition of the microbiome according to this study . Here, twins were treated with NR for 5 months and, in addition to an improved NAD metabolism, there was also an improvement in the composition of the intestinal flora . To be precise, NR increased the presence of Faecalibacterium prausnitzii . This bacterium is associated with better metabolic health and appears to have an anti-inflammatory effect.

Nicotinamide riboside and Parkinson's disease - initial results

Scientists have long suspected that the metabolism of nerve cells plays a role in some neuronal diseases.Decreasing NAD levels could have a negative effect on the mitochondria (the power plants of the cells) and thus influence the performance of our nerve cells. At least that is the hypothesis. One of these neuronal diseases in which nerve cells in the brain die is Parkinson's disease. Here, the dopaminergic neurons in the brain gradually die off, which leads to the typical symptoms.

In order to test their hypothesis, the scientists in the NADPARK study examined 30 patients according to the highest scientific standards (i.e. double-blind, randomized).

Half of the participants were given 1000mg nicotinamide riboside per day for 30 days. In the end, the scientists were able to prove that NR was able to increase NAD levels in the brain. But not only that, the participants with nicotinamide riboside even showed an improvement in their cognitive performance.

This was only a small study, but it clearly shows that even high doses of NR are well tolerated and that there is measurable success. It will certainly not be the last study onnicotinamide riboside and Parkinson's disease.

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 to transport active ingredients directly into the cells and increase bioavailability. However, the study situation here is not yet very good. The higher bioavailability is more of a hypothesis than a proven fact. You can find out more about the various 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 produce nicotinamide riboside chloride . This form of NR is significantly more stable and can therefore increase bioavailability. Nicotinamide riboside chloride is also the ingredient in NIAGEN® . Almost all relevant studies have been carried out with this patented formulation. With the help of the formulation, NIAGEN® can be incorporated into capsules or tablets without losing its effectiveness.

Wusstest Du?

NIAGEN® is the only form of nicotinamide riboside that has been studied multiple times by the FDA, the U.S. Food and Drug Administration, and has been classified asGRAS (generally regarded as safe).

In addition, NIAGEN® has been successfully tested in more than 12 human clinical trials and at least 45 additional studies are on the way.

High homocysteine levels due to NAD precursors

Supplementation with NR can increase NAD levels. At the same time, the researchers found in some studies that homocysteine levels also increased.

Homocysteine is an amino acid whose increased occurrence is considered a proven risk factor for the development of cardiovascular disease. How does this fit together? On the one hand, NR appears to have positive effects on the heart, as 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, with homocysteine, appears to increase a risk factor for the development of arteriosclerosis. The explanation is hidden in the metabolization of the molecule.

Methyl groups as a decisive factor

In order to better understand the homocysteine issue, we need to take a closer look at NAD metabolism. Put simply, there are various ways in NAD metabolism in which we can regenerate NAD from precursor molecules such as NR or NAM. These conversions require so-called methyl groups . These are compounds of carbon and hydrogen atoms that are easily transferable. If we now add more precursors to our body, in our case nicotinamide riboside, then there is an increased conversion of these precursors into NAD. Our desired effect, higher NAD levels, is therefore achieved.

However, the body also needs some methyl groups for this. And this is where homocysteine comes into play. On the 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 is how the researchers explain the result.

Once again summarized as simply as possible. The hypothesis is: The conversion of NR into NAD requires methyl groups. The consumption of methyl groups leads to higher homocysteine levels.

Wusstest Du?

Methyl groups are involved in numerous processes in our body.This also applies to the regulation of our DNA. With the help of mehtyl groups, our body can control which parts of the DNA are read and which are not. Similar to volume controls, certain areas become louder (active) or quieter (inactive). This field of research is called epigenetics.

Betain-TMG - a safe supplement

We have already seen that taking NAD precursors can potentially lead to higher homocysteine levels . It should be noted that this does not necessarily have to be the case. This could not always be proven in the studies and there appears to be a personal predisposition to this.

One possible solution to this problem isto provide the body with more methyl groups. We therefore need a methyl group donor and this is exactly what the molecule betaine can do. There are various forms. Betaine-TMG is the decisive one, because as a methyl group donor it can lower homocysteine levels, 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 and thus has 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). These promising results raise hopes for a longer and healthier lifespan.

Literature

  • Sharma, C., Donu, D., & Cen, Y. (2022). Emerging Role of Nicotinamide Riboside in Health and Diseases. Nutrients, 14(19). Link
  • Zheng, D., Zhang, Y., Zheng, M., Cao, T., Wang, G., Zhang, L., … Peng, T. (2019). Nicotinamide riboside promotes autolysosome clearance in preventing doxorubicin-induced cardiotoxicity. Clinical Science, 133(13). Link
  • Brakedal, Brage et al. “The NADPARK study: A randomized phase I trial of nicotinamide riboside supplementation in Parkinson's disease.” Cell metabolism vol. 34,3 (2022): 396-407.e6. Link
  • Martens, Christopher R et al. “Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.” Nature communications vol. 9,1 1286. 29 Mar. 2018, Link
  • Berven, Haakon et al. “NR-SAFE: a randomized, double-blind safety trial of high dose nicotinamide riboside in Parkinson's disease.” Nature communications vol. 14,1 7793. 28 Nov. 2023, Link
  • Guéant, Jean-Louis et al. “Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials.” Thrombosis and haemostasis vol. 123,3 (2023): 270-282. Link
  • Zhong, Ou et al. “Effects of NAD+ precursor supplementation on glucose and lipid metabolism in humans: a meta-analysis.” Nutrition & metabolism vol. 19,1 20. 18 Mar. 2022, Link
  • Tannous, Cynthia et al. “Nicotinamide Riboside Supplementation Restores Myocardial Nicotinamide Adenine Dinucleotide Levels, Improves Survival, and Promotes Protective Environment Post Myocardial Infarction.” Cardiovascular drugs and therapy, 10.1007/s10557-023-07525-1. 24 Nov. 2023, Link
  • Mehmel M, Jovanović N, Spitz U. Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Nutrients. 2020 May 31;12(6):1616. Link
  • Hong, G., Zheng, D., Zhang, L., Ni, R., Wang, G., Fan, G. C., … Peng, T. (2018). Administration of nicotinamide riboside prevents oxidative stress and organ injury in sepsis. Free Radical Biology and Medicine, 123. Link
  • Bieganowski, P., & Brenner, C. (2004). Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. Cell, 117(4). Link
  • Mehmel, M., Jovanović, N., & Spitz, U. (2020). Nicotinamide Riboside—The Current State of Research and Therapeutic Uses. Nutrients, 12(6). Link
  • Airhart, S. E., Shireman, L. M., Risler, L. J., Anderson, G. D., Nagana Gowda, G. A., Raftery, D., … O’Brien, K. D. (2017). An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers. PLoS One, 12(12). Link

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